Objective To investigate the effect and mechanism of Liuling Jiedu Pills on acute pharyngitis caused by Staphylococcus aureus in rats.Methods The rat model of acute pharyngitis was replicated using the method of injecting 1×109 CFU·mL-1 of Staphylococcus aureus solution into the pharynx of rats.SD rats were randomly divided into a blank group,a model group,a Lanqin Oral Solution group(5 mL·kg-1),and a low-,medium-,and high-dose group of Liuling Jiedu Pills(4.375,8.750,and 17.500 mg·kg-1),with 10 rats in each group.Rats in each group were administered the drug by gavage once a day for 7 days.The general conditions of the rats were observed and recorded every day during the modeling and drug administration periods,and the local inflammation in the pharynx was scored;histopathological changes in the pharynx of the rats were observed by hematoxylin-eosin(HE)staining;serum interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor α(TNF-α),and tumor necrosis factor-α(TNF-α)were detected by ELISA.Immunohistochemistry and Western Blot were used to detect the protein expression levels of IL-1β,IL-6 and TNF-α in rat pharyngeal tissue.Results Compared with the blank group,rats in the model group had significantly increased pharyngeal erythema,significantly higher inflammation scores(P＜0.01),significantly lower body mass on days 5-7 after modeling(P＜0.05,P＜0.01),significantly higher pathological scores(P＜0.01),significantly higher levels of the serum inflammatory factors IL-1β,IL-6,and TNF-α(P＜0.01),and significantly higher pharyngeal tissues showed significantly higher levels of IL-1β,IL-6,and TNF-α proteins(P＜0.01).Compared with the model group,the pharyngeal erythema was significantly reduced in the Lanqin Oral Solution group and the low-,medium-and high-dose groups of Liuling Jiedu Pills,and the inflammation scores were significantly reduced(P＜0.01),and the serum levels of IL-1β,IL-6,and TNF-α were significantly reduced(P＜0.01);the body mass of the rats in the Lanqin Oral Solution group,and in the medium-and high-dose groups of Liuling Jiedu Pills,were significantly increased on the seventh day of the modeling(P＜0.01);the histopathological scores and the levels of IL-1β,IL-6 and TNF-α proteins in pharyngeal tissue were significantly decreased(P＜0.05,P＜0.01).Conclusion Liuling Jiedu Pills can significantly improve the symptoms and inflammatory pathological changes of pharyngeal tissues in rats with acute pharyngitis,and its mechanism may be related to the down-regulation of the expression levels of inflammatory factors such as IL-1β,IL-6,and TNF-α.
Objective The identification of Santali Albi Lignum and its common counterfeits Osyris lanceolata Lignum,Santalum spicatum Lignum was studied to provide experimental basis for the authenticity of this medicinal herb.Methods The identification was carried out using morphological,microscopic,and thin-layer identification methods.The volatile oil of Santali Albi Lignum and its counterfeits were extracted by steam distillation and the volatile oil components were analyzed by gas chromatography-mass spectrometry(GC-MS).The differences of volatile oil components among the three were compared.Results Santali Albi Lignum and its common counterfeits all possessed a sandalwood aroma,but Santali Albi Lignum has abundant oiliness and strong aroma.Osyris lanceolata Lignum aroma exhibits slightly strong odor and slightly camphor flavor,and the smell of Santalum spicatum Lignum is sweet and fragrant.Santali Albi Lignum is greyish-yellow to yellowish-brown in color,while Osyris lanceolata Lignum is generally reddish brown in color,Santalum spicatum Lignum is light yellow to light yellowish-brown,but its surface shows reddish-brown when exposed to air for a long time.In the transection section,the ray width of Santali Albi Lignum is more than 1-2 rows of cells,with occasional 3 rows of cells.The ray width of Osyris lanceolata Lignum is 1-3 rows of cells,while the ray width of Santalum spicatum Lignum is 1-2 rows of cells,mostly uniseriate.In the tangential section,the wood ray of Santali Albi Lignum has a height of 5-15 cells,the wood ray of Osyris lanceolata Lignum has a height of 4-10 cells,while the wood ray of Santalum spicatum Lignum has a height of 4-16 cells.In the radial section,fewer calcium oxalate crystal was found in Santali Albi Lignum,more calcium oxalate crystal was appeared in Osyris lanceolata Lignum,more and larger calcium oxalate crystal was identified in Santalum spicatum Lignum.Genuine and fake sandalwood can be distinguished using sandalwood oil as the thin-layer chromatographic reference.And the volatile oil content of fake Osyris lanceolata Lignum and Santalum spicatum Lignum is lower than that of Santali Albi Lignum.The main components of Santali Albi Lignum are α-santalol and β-santalol.The low content of santalol has been found in Osyris lanceolata Lignum,while α-santalol is extremely low in Santalum spicatum Lignum oil and β-santalol has not been found.Conclusion There are small differences among Santali Albi Lignum and its adulterants in characteristics,microscopical characteristics.But the differences have been found in three-way cross section,thin layer chromatography,volatile oil content and composition characteristics,which can be used for identification of Santali Albi Lignum and its counterfeits.
Objective To observe the effects of tetrandrine on the proliferation,migration,and invasion of melanoma cell B16,and to explore its effects on epithelial mesenchymal transition(EMT)and potential regulatory mechanisms.Methods(1)The proliferation of B16 cells was detected by CCK-8 assay after 0,2,4,6,8 and 10 μmol·L-1 of tetrandrine intervention for 24 and 48 hours.The colony formation ability of B16 cells was detected by plate clone formation assay after 1,2 and 4 μmol·L-1 of tetrandrine intervention;the migration and invasion ability of B16 cells was detected by cell scratch assay and Transwell invasion assay;the expressions of N-cadherin,Vimentin and E-cadherin related to EMT in B16 cells were detected by Western Blot assay.The mouse melanoma lung metastasis model was replicated by tail vein injection of B16 cells to observe the effects of tetrandrine(50 and 100 mg·kg-1)administered by gavage on the number of metastatic tumor nodules in the lungs of mice.(2)The CTD,SwissTargetPrediction and Similarity Ensemble Approach databases were used to predict the targets of tetrandrine;the GeneCards database was used to search for targets related to melanoma disease;the intersection of these two databases was taken as the potential target of tetrandrine for melanoma treatment.The intersected targets were imported into STRING database to construct protein-protein interaction(PPI)network and screen the core targets;the intersected targets were imported into DAVID database for GO function and KEGG pathway enrichment analysis;and molecular docking between tetrandrine and the core targets was verified by Autodock software.(3)In vivo experimental validation:after intervention of 1,2 and 4 μmol·L-1 tetrandrine,Western Blot method was used to detect the expression of the key pathway AKT/NF-κB/CREB pathway-related proteins;and AKT agonist SC79 was used to validate the replication experiments.Results(1)The IC50 of B16 cells intervened by tetrandrine was 4.273 and 4.085 μmol·L-1 at 24 and 48 hours.Compared with the control group,the colony forming ability,scratch healing rate and invasion rate of cells in the 1,2 and 4 μmol·L-1 tetrandrine group were all significantly reduced(P＜0.05,P＜0.01,P＜0.001);the expressions of cellular Vimentin and N-cadherin protein expressions were significantly down-regulated(P＜0.01,P＜0.001),and E-cadherin protein expression was significantly up-regulated(P＜0.01,P＜0.001).Compared with the model control group,the number of melanoma lung metastatic nodules was significantly reduced in the mice in the high-dose group of tetrandrine(P＜0.05).(2)A total of 60 potential targets were obtained for the treatment of melanoma with tetrandrine;core targets such as AKT1,TNF,CCND1,RELA,CASP9,CHUK,and CREBBP were further screened,among which AKT1 was the most strongly interacting target;the signaling pathways such as apoptosis,FoxO,TNF,PI3K-AKT,and NF-κB were mainly involved.The molecular docking showed that tetrandrine had strong binding activity with AKT1,TNF,RELA and other core targets.Compared with the control group,protein expressions of p-AKT/AKT,p-NF-κB p65/NF-κ B p65,and p-CREB/CREB were significantly down-regulated in the cells of the tetrandrine 1,2,and 4 μmol·L-1 groups(P＜0.05,P＜0.01);protein expressions of p-AKT and p-NF-κB p65 were significantly up-regulated in the cells of the SC79 group(P＜0.001).Compared with the SC79 group,protein expressions of p-AKT,p-NF-κB p65,and p-CREB were significantly down-regulated in the cells of the 2 μmol·L-1 tetrandrine+ SC79 group(P＜0.001).Conclusion Tetrandrine may inhibit the proliferation,migration,invasion and EMT of mouse melanoma by regulating the AKT/NF-κB/CREB pathway,and thus inhibit the lung metastasis of mouse melanoma.
Objective To summarize the core prescription for treating metabolic syndrome by academician TONG Xiaolin and explore the intervention mechanism.Methods Outpatient medical records of TONG Xiaolin's treatment for metabolic syndrome were input into the Ancient and Modern Medical Records Cloud Platform for data mining,then the core prescription was extracted.The effective components and therapeutic targets of the core prescription,and metabolic syndrome-related genes were obtained from relevant databases.The core targets were screened out by protein-protein interaction network.The network of core prescription-core compound-core target was constructed.Pathway enrichment analyses were carried out based on the core targets.Results A total of 1 028 records were enrolled and analyzed.The core prescription consists of 10 Chinese medicinals,such as Coptidis Rhizoma,Anemarrhenae Rhizoma,Paeoniae Radix Rubra,etc..The prescription was modified with three-herb formulas,which was composed of Fritillariae Thunbrgii Bulbus,Curcumae Rhizoma and Notoginseng Radix et Rhizoma.A total of 151 active compounds and 64 potential targets for metabolic syndrome of the core prescription were obtained.The core compounds included isorhamnetin,calycosin,berberine and monacolin K.The core targets were MAPK3,MAPK8,and LDLR.The PI3K-Akt,AGE-RAGE and MAPK signaling pathways were involved.Conclusion The core prescription of academician TONG Xiaolin's treatment for metabolic syndrome was composed of Coptidis Rhizoma,Anemarrhenae Rhizoma.The prescription was modified according to symptoms in the form of three-herb formulas.The core prescription may exert its effect by regulating PI3K-Akt,AGE-RAGE,MAPK and other signaling pathways,which could reflect the characteristics of Chinese herbal compound,such as multi-component,multi-target,multi-pathway,and comprehensive regulation.
Objective To investigate the anti-inflammatory effect and mechanism of sappanone A(SA)on lipopolysaccharide(LPS)-induced RAW264.7 cell model based on JAK2-STAT3 signaling pathway.Methods MTT assay was used to detect the effects of sappanone A,LPS and AG490 on RAW264.7 cell viability.The LPS-induced inflammatory model in RAW264.7 cells was established,and the secretion level of interleukin-6(IL-6)in the supernatant was detected by ELISA.mRNA expressions of IL-6,Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)were tested by RT-PCR.The protein expressions of JAK2,phosphorylated JAK2(p-JAK2),STAT3 and phosphorylated STAT3(p-STAT3)were determined by Western Blot.Results Compared with control group,IL-6 secretion level was significantly increased,mRNA expressions of IL-6,JAK2 and STAT3 were up-regulated,and protein expressions of p-JAK2 and p-STAT3 were increased(all P＜0.01)in model group.Compared with model group,high-dosed sappanone A(5 μg·mL-1)was significantly decreased the secretion of IL-6,down-regulated the mRNA expressions of IL-6,JAK2 and STAT3,and inhibited the protein expressions of p-JAK2 and p-STAT3(all P＜0.01).Conclusion Sappanone A may play an anti-inflammatory role by inhibiting the JAK2-STAT3 signaling pathway and hence inhibiting the secretion of IL-6.
Objective To investigate the protective mechanism of Wenyang Fuyuan Prescription on nerve injury by improving brain iron metabolism in rats with cerebral ischemia-reperfusion injury(CIRI)based on ferroptosis.Methods A total of 72 SD rats were randomly divided into sham-operation group,CIRI model group,Wenyang Fuyuan Prescription group(18.0 g·kg-1,gavage),ferroptosis inducer group(100 mg·kg-1,intraperitoneal injection),Wenyang Fuyuan Prescription(18.0 g·kg-1,gavage)+ ferroptosis inducer group(intraperitoneal injection)and ferroptosis inhibitor group(5 mg·kg-1,intraperitoneal injection),12 rats in each group.All the procedures adopted in the sham group were the same as those in the model group.But nylon thread was inserted into the internal carotid artery at a depth of 9 mm and un-plugged middle cerebral artery.The rest of the groups were used to construct middle cerebral artery occlusion/reperfusion(MCAO/R)model by thread embolism method.Ferroptosis inducer(100 mg·kg-1)and ferroptosis inhibitor(5 mg·kg-1)were administered intraperitoneally to rats according to the grouping 24 hours before modeling.Wenyang Fuyuan Prescription(18.0 g·kg-1)was administered by gavage 2 hours after anesthesia and awakening.All intervention were given once daily for 7 consecutive days.The Longa scoring standard was used to evaluate the neurological deficit on 1,3,and 7 days after MCAO/R surgery,respectively.At the end of the treatment period,brain tissues were taken to observe the morphological changes of rat neurons in each group by hematoxylin eosin staining(HE).The ultrastructural changes of neuron mitochondria in each group were observed by transmission electron microscope.The biochemical kit was used to detect the content of iron ions(Fe2+)and reduced glutathione(GSH)in brain tissue.The protein and mRNA expressions of transferrin receptor 1(TFR1),iron regulatory protein 1(IRP1)and ferroportin(FPN)were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and Western Blot.Results① Compared with sham group,the neurological deficit scores of rats in model group increased at each time point(P＜0.01).HE staining showed neurons were sparse and disordered,the nuclei underwent pyknosis,and vacuoles appeared at the edges.Under electron microscopy,it was observed that the number of neuronal mitochondria decreased,the density of mitochondrial membranes increased,massive numbers of mitochondrial membranes ruptured and dissolved,and mitochondrial cristae disappeared.The content of Fe2+,both mRNA and protein expressions of TFR1 were significantly increased(P＜0.01),while GSH content,as well as expressions of mRNA and protein for IRP1 and FPN were significantly decreased(P＜0.05,P＜0.01).② Compared with the model group,the neurological deficit scores of rats in the Wenyang Fuyuan Prescription group decreased at various time points(P＜0.05).The number of neurons increased,their arrangement was relatively neat,the morphology of the nucleus is complete and clear,the mitochondrial structure of neurons was relatively complete,the mitochondrial membrane was relatively intact,and the mitochondrial cristae were clear.The content of Fe2+,both mRNA and protein expressions of TFR1 were decreased(P＜0.05,P＜0.01),while GSH content,as well as expressions of mRNA and protein for IRP1 and FPN increased(P＜0.05,P＜0.01).③ Compared with the Wenyang Fuyuan Prescription group,the neurological deficit scores of rats in ferroptosis inducer group and the Wenyang Fuyuan Prescription + ferroptosis inducer group increased at all time points(P＜0.05).Distribution of neurons was in disorder,the nucleus shrinked,and vacuoles appeared at the edges.The density of mitochondrial membranes increased,some ruptured and dissolved mitochondrial membranes were found.The number of mitochondria decreased and mitochondrial cristae disappeared.The content of Fe2+,both TFR1 mRNA and protein expression increased(P＜0.05,P＜0.01),while the content of GSH,as well as expressions of mRNA and protein for IRP1 and FPN decreased(P＜0.05,P＜0.01).However,there was no statistically significant difference in all observed indicators between the ferroptosis inhibitor group and the Wenyang Fuyuan Prescription group(P＞0.05).Conclusion Wenyang Fuyuan Prescription can improve the neurological function and pathological damage of CIRI rats.Its mechanism may be related to regulating the expression of IRP1 protein,improving the brain iron metabolism pathway,and inhibiting ferroptosis.
Objective To investigate the effects of Rehmanniae Radix before and after processing on the intestinal flora of rats with kidney yin deficiency syndrome.Methods SD rats were randomly divided into blank group,model group,probiotic group(0.35 g·kg-1),high-/medium-/low-dose groups of Rehmanniae Radix Praeparata(3.5,1.75,0.875 g·kg-1),and high-/medium-/low-dose groups of Rehmanniae Radix(3.5,1.75,0.875 g·kg-1),with 9 rats in each group.Except for the blank group,rats in each group were injected intramuscularly with Dexamethasone Sodium Phosphate Injection(0.35 mg·kg-1)once a day for 21 days.The drug was administered by gavage once a day on the seventh day of modelling for 14 days.The adrenal histopathological changes were observed by using HE staining;the levels of serum cyclic adenosine monophosphate(cAMP),cyclic guanosine monophosphate(cGMP),corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),and corticosterone(CORT)were detected by ELISA;and the levels of short-chain fatty acids in the feces and changes in the diversity of intestinal flora were detected by a targeted metabolomic approach in conjunction with 16SrRNA sequencing in the rats in each group.Results(1)Compared with the blank group,the body mass of rats in the model group was significantly decreased on days 7,14 and 21(P＜0.05,P＜0.01);serum levels of cAMP,CRH,ACTH,CORT and the cAMP/cGMP ratio were all significantly increased(P＜0.01),and the cGMP content was significantly decreased(P＜0.01);and the adrenal cortex was thinned,with the boundaries of various layers of the cortex unclear.Compared with the model group,the body mass of rats in the Rehmanniae Radix Praeparata administration group on day 21 were all significantly increased(P＜0.05,P＜0.01),and the serum content of cAMP,CRH,ACTH,CORT and the cAMP/cGMP ratio were all significantly decreased(P＜0.05,P＜0.01),and the content of cGMP was significantly increased(P＜0.05,P＜0.01)in the rats;body mass of rats in the Rehmanniae Radix administration group did not change significantly(P＞0.05),CRH and CORT contents in serum of rats in the high-dose group of Rehmanniae Radix were significantly reduced(P＜0.01),and ACTH contents in serum of rats in the medium-dose group of Rehmanniae Radix were significantly reduced(P＜0.05);the adrenal cortex of rats in all the administration groups were improved,in particular,the thickening of the adrenal cortex layers was obvious in the Rehmanniae Radix Praeparata group,and the improvement effect was superior to that in the Rehmanniae Radix group.(2)Compared with the blank group,the difference of Coverage index was not statistically significant(P＞0.05),and the coverage of each group was good;the abundance index(Sobs,Ace,Chao)and diversity index(Shannon)of the model group were significantly increased(P＜0.01),and the Simpson index was significantly decreased(P＜0.01).Compared with the model group,Sobs index was significantly decreased in the medium-and high-dose groups of Rehmanniae Radix Praeparata(P＜0.05),Chao index was significantly decreased in the administered groups of Rehmanniae Radix Praeparata and high-dose group of Rehmanniae Radix(P＜0.05,P＜0.01),and Simpson index was significantly increased in the high-dose group of Rehmanniae Radix Praeparata(P＜0.05).The changes of Rehmanniae Radix on the richness and diversity of intestinal microbial community in kidney yin-deficient rats were small,while Rehmanniae Radix Praeparata could better maintain the stability of the richness and diversity of intestinal microbial community in kidney yin-deficient rats.(3)Compared with the blank group,the abundance of phylum firmicutes in the feces of the model group was significantly decreased,while the abundance of bacteroides and actinomycetes was significantly increased.The abundance of Lactobacillus was significantly decreased(P＜0.01),while the abundance of norank_f__Muribaculaceae and Bifidobacterium was significantly increased(P＜0.01).Compared with the model group,the trend of recovery of bacterial abundance in the probiotic group and the high-dose group of Rehmanniae Radix Praeparata was more similar to that of the blank group,which showed that it had the best regulating effect on the ratio of bacterial flora;the abundance of lactobacillus in all administered groups was increased,with that of the probiotic group was significantly increased(P＜0.01);the abundance of norank__f__Muribaculaceae and Bifidobacterium were all decreased,among which the probiotic group and the medium-and high-dose groups of Rehmanniae Radix Praeparata were significantly decreased(P＜0.01),and the effect was significantly superior to that of Rehmanniae Radix.The COG functions of the samples in each group were mainly focused on amino acid transport and metabolism,carbohydrate transport and metabolism,translation,ribosomal structure and biogenesis,replication,recombination and repair,but the abundance information of each function was different between groups,which may be due to the differences caused by dysbiosis of intestinal flora.(4)Compared with the blank group,the levels of acetic acid,butyric acid and propionic acid in the faeces of rats in the model group were significantly decreased(P＜0.05,P＜0.01),and the level of isobutyric acid was significantly increased(P＜0.01).Compared with the model group,the levels of acetic acid,butyric acid and propionic acid in the faeces of rats in the probiotic group and the low-,medium-and high-dose groups of Rehmanniae Radix Praeparata were significantly increased(P＜0.05,P＜0.01)and the levels of isobutyric acid were significantly decreased(P＜0.05,P＜0.01);although the above indexes in the Rehmanniae Radix group were improved,the difference was not statistically significant(P＞0.05).Conclusion The enhanced therapeutic effect of Rehmanniae Radix after processing on rats with kidney yin deficiency syndrome may be related to its adjusting effect on intestinal flora.
Objective To observe the clinical effect of Yi'naokang Capsules combined with Donepezil Hydrochloride Tablets in treating post-stroke cognitive impairment(PSCI).Methods 110 patients who met the diagnostic criteria of PSCI in the outpatient department were included.According to the random number table method,the patients were divided into trial group and control group,with 55 cases in each group.Patients in control group were treated with routine western medicine,including the treatment of Donepezil Hydrochloride Tablets and secondary prevention of stroke such as lowering blood pressure,lowering blood lipid,lowering blood glucose and anti-platelet aggregation.The trial group was treated with Yi'naokang Capsules on the basis of the treatment in control group,and both groups were treated for 6 months.Before and after 6 months of treatment,the cognitive function of patients was evaluated by the Montreal Cognitive Assessment(MoCA)scale.The activity of daily living(ADL)scale was used to evaluate the ability of daily living,and the severity of cerebral white matter lesions was evaluated by Fazekas scale,and the adverse reactions were also observed.Results After 6 months of treatment,the total score of the MoCA,the scores of visual space and executive function,attention,delayed recall and the ADL of the two groups were all improved(P＜0.05),and the improvement degree of the trial group was better than that of the control group(P＜0.05).The Fazekas score of the trial group after treatment was no significant difference when compared with that before treatment(P＞0.05),but it increased in the control group after treatment(P＜0.05),and the effect of delaying white matter lesion in the trial group was better than that in the control group(P＜0.05).Conclusion Yi'naokang Capsules combined with Donepezil Hydrochloride Tablets are superior to Donepezil alone in the treatment of PSCI,which can safely and effectively improve the cognitive function and daily living ability of patients,as well as prolong the progress of white matter lesions.
Objective To explore the mechanism of Gusong Yigu Decoction(inchuding Astragali Radix,Codonpsis Radix,Angelicae Sinensis Radix,etc.)in the treatment of postmenopausal osteoporosis(PMOP)based on network pharmacology and animal experiment.Methods The effective ingredients and corresponding targets of Gusong Yigu Decoction were collected by using TCMSP database.GeneCards,TTD,and other databases were used to collect PMOP target proteins.R language was used to obtain the intersection targets and draw Wayne diagram.STRING database was used for the establishment of protein-protein interaction network.At last,GO function enrichment and KEGG pathway enrichment were performed on all common targets.The ovariectomized SD rats were used in the animal experiment.Gusong Yigu Decoction was administered by gavage for 12 weeks.The changes of bone histomorphology were detected by HE staining,the mRNA and protein levels of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(Akt)in bone tissue of proximal tibial were tested by qRT-PCR and Western Blot,respectively.Results A total of 91 effective ingredients of Gusong Yigu Decoction in the treatment of PMOP,70 common targets of drugs-diseases were obtained.GO enrichment analysis mainly included DNA-binding transcription activator activity,RNA polymerase II-specific,ubiquitin protein ligase binding.KEGG pathway enrichment analysis included PI3K/Akt signaling pathway,TNF signaling pathway,and apoptosis.The animal experiment showed that bone histomorphology was significantly improved,meanwhile the mRNA and protein expressions of PI3K and Akt were significantly increased in Gusong Yigu Decoction group(P＜0.01).Conclusion Gusong Yigu Decoction may improve bone microstructure through multiple channels and targets.Gusong Yigu Decoction can increase the number and thickness of bone trabeculae and reduce the separation of bone trabeculae by activating PI3K/Akt signaling pathway,and thus play an anti-osteoporosis role in postmenopausal osteoporosis.
Objective To study the effect and its mechanism of hederagenin(hed)on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice.Methods(1)In vitro experiments:after treating RAW264.7 cells with different concentrations(0,2.5,5,10,20,40 μmol·L-1)of hed for 24 hours,the cell survival rate was detected by MTT assay.RAW264.7 cells were divided into:blank group,lipopolysaccharide(LPS)group(1 μg·L-1),LPS+2.5 μmol·L-1 hed group,LPS+5 μmol·L-1 hed group and LPS+10 μmol·L-1 hed group;an in vitro cellular inflammation model was established using LPS intervention for 24 hours and co-incubated with hed for 24 hours.The levels of interleukin 1β(IL-1β),IL-6 and tumor necrosis factor α(TNF-α)in the cell supernatant were determined by ELISA;the expression levels of TLR4/NF-κB pathway-related proteins in the cells were detected by Western Blot.(2)In vivo experiments:C57BL/6 mice were randomly divided into a blank group,a model group,a Salazosulfapyridine group(200 mg·kg-1),and an hed low-,medium-,and high-dosage groups(12.5,25,and 50 mg·kg-1),with 5 mice in each group.Mice were induced to establish UC model by drinking 3%DSS solution freely for 7 days.The UC model was then established by gavage once a day for 7 days.At the end of the administration,the Disease Activity Index(DAI)was evaluated;pathological changes in the colonic tissues of mice were observed by HE staining;the levels of IL-1β,IL-6,and TNF-α in the colonic tissue were measured by ELISA;and the expression levels of proteins related to the TLR4/NF-κB pathway in the colonic tissue were detected by Western Blot.Results(1)In vitro experiments:compared with the blank group(0 μ mol·L-1 group),there was no significant change in the cell survival rate in the 2.5-10 μmol·L-1 hed group(P＞0.05),and there was no significant toxicity effect on RAW264.7 cells.Compared with the blank group,the expression levels of IL-1β,IL-6,and TNF-α in RAW264.7 cells in the LPS group were significantly increased(P＜0.01);and the protein expression levels of TLR4 and p-NF-κ B/NF-κ B were significantly increased(P＜0.01).Compared with the LPS group,the expression levels of IL-1β and TNF-α in RAW264.7 cells in the hed 2.5,5,and 10 μmol·L-1 concentration groups were significantly decreased(P＜0.05,P＜0.01),and the protein expression levels of TLR4,p-NF-κB/NF-κB were significantly decreased(P＜0.05,P＜0.01);the IL-6 expression level of RAW264.7 cells in the hed 5 and 10 μmol·L-1 concentration groups was significantly reduced(P＜0.05,P＜0.01).(2)In vivo experiments:compared with the blank group,the body mass of mice in the model group was consistently reduced(P＜0.01),the DAI score was significantly elevated(P＜0.01),and the length of the colon was significantly shortened(P＜0.01);the colonic tissue showed obvious epithelial cell damage,and the histopathological scores were significantly elevated(P＜0.01);and the expression levels of the pro-inflammatory cytokines IL-1β,IL-6 and TNF-α were significantly increased(P＜0.01);protein expression levels of TLR4 and p-NF-κB/NF-κB were significantly increased(P＜0.01)in colon tissue.Compared with the model group,the body mass of mice in the low-,medium-and high-dose groups of hed were significantly increased(P＜0.05,P＜0.01),the DAI score was significantly decreased(P＜0.05,P＜0.01),the pathological damage of colon tissue improved to different degrees,and the protein expression levels of TLR4,p-NF-κB/NF-κB in the colonic tissue were significantly decreased(P＜0.05,P＜0.01);the colon length of mice in the medium-and high-dose groups of hed were significantly increased(P＜0.05,P＜0.01),and the expression levels and histopathological scores of IL-1β,IL-6,and TNF-α in colon tissue were significantly reduced(P＜0.05,P＜0.01).Conclusion Hed were able to effectively ameliorate colonic histopathological injury and reduce the levels of inflammatory factors in DSS-induced UC mice,and their mechanism of action may be related to the inhibition of the TLR4/NF-κB pathway.
Objective To analyze the heat-clearing and anti-inflammatory mechanism of Xiaoyan Tuire Granules by network pharmacology,and to determine the 8 main active components of Xiaoyan Tuire Granules by ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS/MS).Methods SwissTargetPrediction database was used to screen the target of components absorbed in the blood of Xiaoyan Tuire Granules.The main target of disease was obtained by CTD database,and the protein-protein interaction(PPI)was analyzed by String platform.GO and KEGG enrichment analysis were conducted using the DAVID database,followed by the construction of the components-targets-pathways network using Cytoscape software.Finally,the molecular docking verification of the key compound-target was conducted.The main active components in Xiaoyan Tuire Granules,including indirubin,isoliquiritigenin,liquiritigenin,glycyrrhizinic acid,liquiritin,esculetin,caffeic acid and chlorogenic acid,were determined by UPLC-MS/MS method.Analysis was performed on a WATERS ACQUITY UPLC® BEH C18 column(2.1 mm×100 mm,1.7 μm)with gradient elution of 0.1%formate in acetonitrile(A)-0.1%formate-5 mmol·L-1 ammonium formate(B),and the determination was carried out in multiple reaction monitoring(MRM)mode.Results Sixteen potential active components,such as indirubin,esculetin,and caffeic acid were identified by network pharmacology and molecular docking,and 10 core targets including transcription factor AP-1(JUN),adhesive connexin β1(CTNNB1)and cysteine aspartic protease-3(CASP3)were predicted.The pathway enrichment analysis revealed that heat-clearing and anti-inflammatory effects of Xiaoyan Tuire Granules were mainly related to signaling pathways such as interleukin-17(IL-17)and hypoxia-induced cause-1(HIF-1).Molecular docking experiments showed that its main active components docked well with core targets.The results of content determination exhibited that all components had good linear relationship within certain concentration range(r＞0.999),good precision,repeatability,and stability.The contents of 8 components in 16 batches of samples were 0.94-3.41,0.99-5.61,0.80-5.84,85.48-141.11,4.30-10.09,152.35-271.80,11.31-26.94,1.99-5.58 μg·g-1,respectively.The contents of indirubin,isoliquiritigenin,liquiritigenin,liquiritin,and chlorogenic acid in Xiaoyan Tuire Granules from two manufacturers were significantly different.Conclusion This study preliminarily revealed the mechanism of Xiaoyan Tuire Granules,which exerted heat-clearing and anti-inflammatory effects through multiple components,targets and pathways.A method for the determination of multiple components in Xiaoyan Tuire Granules was established.This study may provide a reference for its pharmacological research and quality control.
Objective To investigate the impact of usnic acid on neuronal necroptosis in rats with cerebral infarction by regulating the receptor-interacting protein kinase 1(RIPK1)/receptor-interacting protein kinase 3(RIPK3)/mixed lineage kinase domain-like protein(MLKL)signaling pathway.Methods The rat model of cerebral infarction was established by middle cerebral artery occlusion and reperfusion(MCAO/R).The successfully modeled rats were divided into model group,NEC-1(RIP1 inhibitor)group,low-,medium-,and high-dose of usnic acid groups,with 20 rats in each group.Another 20 rats were selected as a sham-operation group.After 3 days of drug intervention,the modified Neurological Severity Scale(mNSS)was applied to evaluate the degree of neurological damage of rats in each group.TTC staining was applied to detect the volume of cerebral infarction.HE staining was selected to observe pathological damage in brain tissue.PI/NeuN staining was selected to observe neuronal necrosis.RT-qPCR was used to detect mRNA levels of RIPK1,RIPK3 and MLKL in rat ischemic brain tissue.Western Blot was used to determine the expressions of RIPK1/RIPK3/MLKL signaling pathway related proteins in rat ischemic brain tissue.Results Compared with the sham-operation group,the neural cells in the model group showed structural damage,cell disrupted,deformation,and nuclear pyknosis,furthermore,the mNSS score,the cerebral infarction volume,proportion of PI-positive neurons were significantly increased(P＜0.05).The mRNA levels of RIPK1,RIPK3,MLKL in brain tissue,ratio of p-RIPK1/RIPK1,and the levels of RIPK3 and MLKL proteins were obviously increased(P＜0.05).Compared with the model group,the damage degree of neurocyte morphology in the low-,medium-,and high-dose of usnic acid groups was gradually alleviated,the nuclear membrane was gradually became clear,and the cell body was gradually returned to normal.The neurocyte morphology in the NEC-1 group was basically intact,and the nuclear membrane was basically clear.The mNSS score,cerebral infarction volume and proportion of PI-positive neurons in NEC-1 group and usnic acid groups were significantly decreased(P＜0.05).The mRNA levels of RIPK1,RIPK3,MLKL,ratio of p-RIPK1/RIPK1,and levels of RIPK3 and MLKL proteins in brain tissue were obviously reduced in usnic acid groups and NEC-1 group.Also,there was dose-dependent decrease in usnic acid groups(P＜0.05).No statistically obvious difference was found between the high-dose usnic acid group and the NEC-1 group(P＞0.05).Conclusion Usnic acid inhibits neuronal necroptosis in rats with cerebral infarction by inhibiting the RIPK1/RIPK3/MLKL signaling pathway,thereby alleviating brain injury in rats with cerebral infarction.
Objective To explore the effect and potential mechanism of Huayu Mingmu Recipe(HMR)-containing serum on high glucose-induced angiogenesis of human retinal microvascular endothelial cells(HRMECs).Methods CCK-8 method is used to screen the optimal sugar concentrations,as well as volume fraction of drug-containing serum.A model of high glucose-induced HRMECs dysfunction was established.The HRMECs were divided into 6 groups such as normal control group which was treated with normal ECM culture medium(containing 5.5 mmol·L-1 glucose)and 10%blank serum,the mannitol control group and the high glucose model were given 19.5 mmol·L-1 mannitol and 19.5 mmol·L-1 D-glucose on the basis of the treatment of normal control group,respectively.The low-,medium-,and high-dose groups of HMR were given 10%low-,medium-,and high-dose medicated serum(without blank serum)on the basis of the model group.The colony experiment was used to detect the number of cell colonies.Transwell experiment was used to test the number of cell migration,and tube formation experiment was used to determine the forming of tubes.Immunofluorescence,Western Blot and RT-PCR were used to detect levels of protein and mRNA expression of FactorⅧ,platelet endothelial cell adhesion molecule-1(CD31),cell differentiation factor(CD34),vascular endothelial growth factor A(VEGFA),vascular endothelial growth factor receptor 2(VEGFR2).Results Compared with the normal control group,the model group could promote colony formation of HRMECs(P＜0.01),cell migration(P＜0.01),and lumen formation(P＜0.01).The levels of protein and mRNA expressions of Factor VIII,CD31,CD34,VEGFA,VEGFR2 were significantly increased(P＜0.01)in model group.Compared with the model group,low-,medium-and high-dose HMR-containing serum groups could inhibit colony formation of HRMECs(P＜0.05,P＜0.01),cell migration(P＜0.01),and lumen formation(P＜0.05,P＜0.01).The levels of protein and mRNA expressions of Factor VIII,CD31,CD34,VEGFA,VEGFR2 were significantly reduced(P＜0.05,P＜0.01)in HMR-containing serum groups.There was no statistically significant difference in results of various tests between the normal control group and the mannitol control group(P＞0.05).Conclusion HMR-containing serum can inhibit the proliferation,migration,and tube formation of HRMECs induced by high glucose,and then prevent or reduce angiogenesis.The mechanism may be related to the regulation of VEGFA/VEGFR2 signaling pathway.
Objective To explore the role and mechanism of puerarin in ameliorating acetaminophen(APAP)-induced acute liver injury in mice based on ferroptosis signaling pathway.Methods Twenty-four C57BL/6J mice were randomly divided into normal group,model group,and puerarin low-and high-dose groups(50 and 200 mg·kg-1),6 mice in each group;all the administration groups were given continuous gavage(10 mL·kg-1)once a day pre-dosed for 3 days.One hour after the last dose,APAP(300 mg·kg-1)was intraperitoneally injected into the mice of the model group and the puerarin low-and high-dose groups to replicate the drug-induced liver injury(DILI)mouse model.After 24 hours,the serum levels of alanine transaminase(ALT),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH)were measured by the microplate assay;HE staining was used to observe the histopathological changes in liver tissue;the apoptosis of hepatocytes was observed by the TUNEL staining assay;the levels of malondialdehyde(MDA)were measured by the TBA assay;the mRNA expression levels of reactive oxygen species(ROS),4-hydroxynonenal(4-HNE),glutathione peroxidase 4(GPX4),and solute carrier family 7 member 11(SLC7A11)were detected by immunofluorescence;qRT-PCR was performed to measure the mRNA levels of ferroptosis-related genes GPX4,transferrin receptor(TFRC),and solute carrier family 11 member 2(SLC11A2)in liver tissue.Results Compared with the normal group,the serum ALT,AST,and LDH levels of mice in the model group were significantly elevated(P＜0.01);the liver lobules showed obvious damage,with swelling and rupture of hepatocytes,cytoplasmic vacuolisation,fragmentation of nuclei,congestion of the hepatic blood sinusoids and infiltration of inflammatory cells,and an increase in apoptotic cells;the level of MDA in the hepatic tissues was significantly elevated(P＜0.05);the red fluorescence(positive expression)of ROS and 4-HNE was significantly enhanced(P＜0.05,P＜0.01),and the red fluorescence(positive expression)of GPX4 and SLC7A11 was significantly weakened in liver tissue(P＜0.01);the mRNA expressions of GPX4 and SLC11A2 in liver tissue were significantly down-regulated(P＜0.05),and there was a tendency for the down-regulation of TFRC expression but the difference was not statistically significant(P＞0.05).Compared with the model group,the serum AST and LDH levels of mice in the low-and high-dose groups of puerarin were significantly reduced(P＜0.05,P＜0.01),and there was a decrease in serum ALT,but the difference was not statistically significant(P＞0.05);the structure of the liver lobules was clearer,with radial arrangement of hepatic cords,and the area of necrotic liver tissue and apoptotic cells were significantly reduced;the level of MDA in the liver tissue was significantly reduced(P＜0.05);the red fluorescence(positive expression)of ROS and 4-HNE in liver tissue were significantly attenuated(P＜0.05,P＜0.01).The red fluorescence(positive expression)of GPX4 and SLC7A11 in liver tissue of the mice in the puerarin low-dose group were significantly enhanced(P＜0.05,P＜0.01),and there was a tendency to enhance the red fluorescence(positive expression)of GPX4 and SLC7A11 in the liver tissue of the mice in the puerarin high-dose group,but the difference was not statistically significant(P＞0.05).The mRNA expressions of GPX4 and TFRC in liver tissue of mice in low-dose puerarin group was significantly up-regulated(P＜0.05),while the mRNA expressions of GPX4 and SLC11A2 in high-dose puerarin group were significantly up-regulated(P＜0.05).Conclusion Puerarin had a significant protective effect on APAP-DILI,which may be related to its inhibition of cellular ferroptosis through the SLC7A11/GPX4 pathway.
Fibrosis refers to the final outcome of damage in multiple-type tissue and the imbalance of tissue repair especially in the process of chronic inflammatory response diseases.Fibrosis can occur in various organ tissues.Its continuous progression may lead to organ dysfunction and failure,which is a huge threat to human health.Traditional Chinese medicine has significant therapeutic effects in preventing and treating fibrosis.Due to its characteristics of multiple components,pathways,and targets,it has become a hot research topic in the field of fibrosis.Astragali Radix,a Chinese medicinal for supplementing qi,is the root of Astragalus membranaceus(Fisch.)Bge.var.mongholicus Hisao or Astragalus membranaceus(Fisch.)Bge.It has the effects of replenishing qi and elevating yang,generating fluid and nourishing blood,expelling toxin and draining pus,astringing sore and promoting granulation.It has found that Astragali Radix contains many chemical components such as polysaccharides,saponins,and flavonoids,which have good anti-inflammatory and antioxidant effects.Astragali Radix can effectively intervene in the fibrosis process of multiple organ tissues such as the heart,kidney,liver,and lung.Therefore,this article reviews the anti-fibrotic effects and mechanisms of Astragali Radix and its chemical components,hoping to provide ideas and references for the development and utilization of Astragali Radix.
Objective To investigate the effect and mechanism of Huanglian Jiedu Decoction in improving the itching symptoms of 1-chloro-2,4-dinitrobenzene(DNCB)-induced atopic dermatitis(AD)in mice.Methods Thirty-six Balb/c mice were randomly divided into normal group,model group,Dexamethasone(positive control,2.5 mg·kg-1)group and Huanglian Jiedu Decoction low-,medium-and high-dose groups(0.4,0.8 and 1.6 g·kg-1),6 mice in each group.After shaving the back of the mice,200 μL of DNCB solution was applied to the back of the mice for sensitisation(1%DNCB for 3 consecutive days)and excitation(1.5%DNCB,starting from the fourteenth day,excitation was performed once every 3 days for a total of 5 times).The stimulation and drug interventions were carried out simultaneously,and each group was administered by gavage at a set dose once daily for 14 days.The severity score of the skin lesions was calculated with reference to the Scoring Atopic Dermatitis(SCORAD),and the number of times the mice scratched within 20 minutes was recorded.The pathological changes of the lesions were observed by HE staining;mast cell infiltration was observed by toluidine blue staining;and the mRNA expression levels of thymic stromal lymphopoietin(TSLP),interleukin(IL)13,histamine H4 receptor(HRH4),and IL-31 in the lesions were detected by RT-qPCR.Results Compared with the normal group,the dorsal skin of the mice in the model group showed obvious erythema,mossification,crusting and epidermal shedding after DNCB excitation,and the severity score of the lesions was significantly increased(P＜0.001);the hyperkeratosis of epidermis,the thickness of spinous layer was significantly increased(P＜0.001),sponge oedema,and a large number of inflammatory cells infiltration was seen in the dermis;and the number of mast cells was significantly increased(P＜0.001);the times of scratches within 20 minutes was significantly increased(P＜0.01);and the mRNA expression levels of TSLP,IL-13,HRH4,and IL-31 in the skin lesion tissue were all significantly elevated(P＜0.05,P＜0.01).Compared with the model group,the skin lesions on the backs of mice in the low-,medium-and high-dose groups of Huanglian Jiedu Decoction were significantly improved,the mossy area was significantly reduced,the severity was significantly reduced,and the severity score of skin lesions was significantly reduced(P＜0.001),and the number of mast cells and the mRNA expression levels of IL-13,HRH4,and IL-31 were significantly reduced in the skin lesion tissues(P＜0.05,P＜0.01,P＜0.001);the thickness of the stratum spinosum was significantly reduced in the medium-and high-dose groups of Huanglian Jiedu Decoction(P＜0.001),and the number of inflammatory cells in the dermis was significantly reduced;the number of scratching in mice in the high-dose group of Huanglian Jiedu Decoction was significantly reduced within 20 minutes(P＜0.01),and the mRNA expression level of TSLP in the lesion tissue was significantly reduced(P＜0.05).Conclusion Huanglian Jiedu Decoction can alleviate itching symptoms in AD mice,and its mechanism of action may be related to repairing the skin barrier in AD mice,attenuating the infiltration of inflammatory cells and mast cells,and down-regulating the mRNA expressions of itch-associated factors TSLP,IL-13,IL-31 and HRH4 in skin tissues.
Objective A HPLC fingerprint method of Alpiniae Oxyphyllae Fructus(AOF)before and after salt-processing was established,to compare the differences of chemical components between raw and processed AOF combined with chemical pattern recognition.Methods HPLC method was used to establish the fingerprint of raw and salt-processed AOF.Principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were applied to explore the different components of raw and salt-processed AOF in different batches.Results Totally 30 and 32 common peaks in the HPLC fingerprint from the raw and salt-processed AOF were detected,respectively.And 8 of them were identified by comparison with the standards.They were peak X2(5-hydroxymethylfurfural),peak 1(protocatechuic acid),peak 2(protocatechualdehyde),peak 4(epicatechin),peak 21(chrysin),peak 22(kaempferide),peak 25(tectochrysin)and peak 26(nootkatone).The results of PCA and OPLS-DA showed that raw and salt-processed AOF can be grouped into two categories.A total of 12 components,which were considered as differential markers of raw and salt-processed AOF,were screened by method of variable importance in projection(VIP).The 12 components were peak X1,peak 26(nootkatone),peak 16,peak 3,peak X2(5-hydroxymethylfurfural),peak 25(tectochrysin),peak 15,peak 12,peak 8,peak 10,peak 17 and peak 20.Conclusion The combination of HPLC fingerprint and chemical pattern recognition can be used to analyze the quality differences of AOF before and after salt-processing.
Objective To study the effect and potential mechanism of Chaihuang Yishen Granules on renal fibrosis in mice with chronic kidney disease.Methods Thirty-six C57BL/6 male mice were randomly divided into sham group,model group,low-,and high-dose Chaihuang Yishen Granules groups(3.835 g·kg-1 and 7.67 g·kg-1),positive control group and Mincle ligand trehalose-6,6-dibehenate(TDB 10 mg·kg-1)group.Unilateral ureteral obstruction(UUO)was used to establish the model of renal fibrosis in mice.One hour after operation,mice in each drug-treated group were given corresponding drugs by gavage,and sham operation group and model group were given saline by gavage,once a day for 7 consecutive days.The pathological changes and fibrosis in the kidneys of mice in all groups were observed by hematoxylin eosin staining and Sirius red staining.The expressions and secretions of inflammatory factor IL-1β,IL-6 and TNF-α in kidneys of all groups were detected by Real-time PCR and ELISA.Immunohistochemistry and Western Blot were used to detect fibrosis indicators,including α-SMA and Fn protein levels.Immunofluorescence and Western Blot were further used to determine protein levels of Mincle and its downstream signal Syk/NF-κB.The proportion of Mincle positive macrophages was analyzed by flow cytometry.Results Compared with the model group,low-and high-dose Chaihuang Yishen Granules can effectively improve UUO-induced renal injury and fibrosis,and inhibit α-SMA and Fn protein levels in the kidney(P＜0.01).Moreover,high-dose Chaihuang Yishen Granules can effectively reduce the expressions and secretions of inflammatory factor IL-1β,IL-6 and TNF-α of kidney in UUO model(P＜0.01),as well as inhibit phosphorylation of NF-κB(P＜0.01).The mechanism study showed that Chaihuang Yishen Granules could significantly reduce the protein level of Mincle and the activity of its downstream signal Syk in the kidney of UUO mice(P＜0.01).After TDB was used to activate Mincle,the effect of Chaihuang Yishen Granules on improving renal injury,inflammatory factor secretion and fibrosis was significantly reduced(P＜0.05,P＜0.01).Conclusion Chaihuang Yishen Granules can improve UUO-induced renal injury,inflammation and fibrosis,and its mechanism may be related to the down-regulation of Mincle/Syk/NF-κB signaling pathway.
目的 观察南蛇藤提取物通过抑制有氧糖酵解过程对大鼠胃癌前病变(Precancerous lesions of gastric cancer,PLGC)的影响,并探讨其可能机制.方法 采用复合模型复制法构建大鼠胃癌前病变模型,模型复制成功后,随机分为模型组及南蛇藤提取物低、中、高剂量组(12.5、25、50 mg·kg-1),每组 10 只,灌胃治疗持续 4 周后处死大鼠.采用苏木素-伊红(HE)染色观察胃黏膜组织病理学改变,化学比色法检测胃黏膜乳酸含量;免疫组化(IHC)及实时荧光定量聚合酶链反应(Real-time PCR)检测有氧糖酵解标志物己糖激酶 2(HK2)、M2 型丙酮酸激酶(PKM2)、葡萄糖转运蛋白 1(GLUT1)、乳酸脱氢酶A(LDHA)、缺氧诱导因子 1α(HIF-1α)及潜在靶点叉头框蛋白O4(FOXO4)的蛋白和mRNA表达.结果 与模型组比较,不同剂量的南蛇藤提取物能够部分缓解胃癌前病变大鼠胃黏膜的病变;降低大鼠胃黏膜的乳酸含量(P＜0.01);降低HK2、PKM2、GLUT1、LDHA、HIF-1α的蛋白及mRNA表达,提高FOXO4 的蛋白及mRNA表达(P＜0.05,P＜0.01).结论 南蛇藤提取物能够有效改善胃癌前病变大鼠胃黏膜组织病理性改变,纠正大鼠胃黏膜的酸性微环境,其机制可能与抑制有氧糖酵解、上调FOXO4的表达有关.
目的 系统评价加味温胆汤联合黛力新治疗冠心病伴焦虑抑郁状态的有效性及安全性.方法 检索中国知网等国内外 8 大数据库自建库至 2023 年 4 月有关加味温胆汤联合黛力新治疗冠心病伴焦虑抑郁状态的随机对照试验,按照纳入及排除标准筛选文献并提取数据,按Cochrane Handbook 5.1 评价标准对纳入研究进行质量评估,采用RevMan 5.4 软件进行Meta分析.结果 纳入 12 篇文献,共 924 例患者.Meta分析结果显示,与对照组比较,加味温胆汤联合黛力新治疗可明显提高心绞痛有效率[OR=4.23,95%CI(2.44,7.33),P＜0.0001]、中医症候有效率[OR=2.70,95%CI(1.46,4.99),P=0.002]、焦虑有效率[OR=2.71,95%CI(1.52,4.83),P=0.0007]、抑郁有效率[OR=3.33,95%CI(1.51,7.35),P=0.003]、硝酸甘油减停率[OR=4.25,95%CI(1.85,9.78),P=0.007]、心电图有效率[OR=3.27,95%CI(1.19,9.04),P=0.02];降低汉密顿焦虑量表(HAMA评分)[MD=-3.86,95%CI(-4.90,-2.82),P＜0.00001]、汉密顿抑郁量表(HAMD)评分[MD=-4.90,95%CI(-5.75,-4.05),P＜0.00001]、焦虑自评量表(SAS)评分[MD=-3.53,95%CI(-4.71,-2.36),P＜0.00001]、中医症候积分[MD=-4.02,95%CI(-5.59,-2.45),P＜0.00001];升高西雅图心绞痛量表(SAQ)各维度的评分(P＜0.00001);同时可降低白细胞介素 6(1L-6)、肿瘤坏死因子α(TNF-α)、超敏C反应蛋白(hs-CRP),提高 5-羟色胺(5-HT)、脑神经营养因子(BDNF)(P＜0.001),且不良反应发生率亦低于对照组(P=0.002).结论 加味温胆汤联合黛力新治疗在提高冠心病伴焦虑抑郁状态患者的临床有效率、改善心绞痛和焦虑抑郁症状、减轻炎症反应、提高神经递质水平以及安全性等方面均优于单独使用黛力新,值得推荐临床应用.但受纳入研究样本量和文献质量的限制,上述结论尚需更多高质量研究予以验证.
