OBJECTIVES:To elucidate the neuroimmune regulatory mechanism of the circadian rhythm gene KLF10 as a biomarker for anxiety depressive disorder (ADD). METHODS:The differentially expressed circadian rhythm genes were screened using human peripheral blood gene chip data from the GEO database (including 64 healthy individuals, 62 patients with major depressive disorder [MDD], and 59 with ADD) in conjunction with the MSigDB database. Weighted gene co-expression network analysis and machine learning models were employed to identify the core genes, followed by KEGG pathway enrichment analysis and evaluation of their diagnostic efficacy using ROC curves. In a male SD rat model of ADD induced by chronic restraint and corticosterone stress, the changes in depressive-like behaviors, hippocampal and amygdala pathologies, levels of inflammatory and pro-inflammatory cytokines, co-localization of KLF10 and p-p65 expression, and expression levels of NF‑κB/NLRP3 pathway molecules were examined following stereotactic AAV virus injection into the lateral ventricle for KLF10 overexpression. RESULTS:Compared with healthy individuals, the depressive patients showed differential expressions of 9 circadian rhythm genes. Compared with the MDD patients, the patients with ADD had significantly higher immune infiltration scores with upregulated NOD-like receptor and NF‑κB signaling pathways. The specific biomarker KLF10 demonstrated a diagnostic efficacy of 0.885. In the rat models of AOD, KLF10 overexpression significantly ameliorated depression- and anxiety-like behaviors, restored the balance between the pro- and anti-inflammatory cytokines, and improved hippocampal and amygdala pathologies. KLF10 overexpression also markedly upregulated NFKBIA mRNA, downregulated NLRP3 and RELA mRNAs, and reduced protein expressions of p-IκB‑α, p-p65, and NLRP3 in the brain tissues of the rats. CONCLUSIONS:KLF10 overexpression ameliorates ADD behaviors in rats by inhibiting hippocampal-amygdala inflammation via downregulating the NF‑κB/NLRP3 pathway, suggesting the potential of KLF10 as a diagnostic biomarker and therapeutic target for AOD.

BACKGROUND:Anxiety-depressive disorder (ADD) is one of the important subtypes of depression, which has been shown to be closely related to neuroimmune abnormalities. Currently, specific biomarkers have not been identified as diagnostic, differential, and therapeutic targets. This study aimed to explore the molecular mechanisms and diagnostic biomarkers of ADD and elucidate its association with neuroinflammation. METHODS:Differentially expressed circadian rhythm-related genes were screened. Key genes were identified by machine learning. An ADD rat model was established using chronic restraint stress combined with corticosterone administration. Using AAV virus tools for KLF-10 overexpression and knockout (KLF10-OE and shKLF10), depression-like and anxiety-like behaviors were evaluated through behavioral experiments, pathological changes in the hippocampus and amygdala were observed by Nissl staining, cytokine levels were detected by ELISA, molecular co-localization was performed by RNAscope ISH and immunofluorescence, and molecular expression of NF-κB/NLRP3 pathway was detected by Western blot and qRT PCR. RESULTS:Nine circadian rhythm-related genes showed significant differential expression, with KLF10 identified as a diagnostic biomarker. KLF10 overexpression ameliorated depressive-like and anxiety-like behaviors, and reduced pro-inflammatory factors (IL-1β, TNF-α) and increased anti-inflammatory factors (IL-10, TGF-β) in both brain and serum, the treatment can be blocked by PMA. KLF10 suppressed IκB-α phosphorylation-mediated NF-κB nuclear translocation and inhibited downstream molecules. CONCLUSION:KLF10 mitigates hippocampal-amygdala neuroinflammation by downregulating the NF-κB/NLRP3 pathway, thereby alleviating a ADD symptoms, and represents a potential diagnostic biomarker and therapeutic target.

BACKGROUND:Stroke patients are prone to gastrointestinal dysfunction, with a significantly higher risk of fecal incontinence (FI), which severely affects their quality of life. AIMS:We investigated the incidence and associated risk factors of FI in stroke patients. SUMMARY OF REVIEW:Stroke patients who met the inclusion and exclusion criteria were consecutively recruited at one university medical center from January 2022 to December 2024. FI occurred in 220 of 1359 stroke patients (16.19%). Logistic regression analysis revealed that age, gender, cognitive impairment, National Institutes of Health Stroke Scale (NIHSS) admission score, antibiotic use, and gavage feeding were closely associated with FI incidence in stroke patients. Subsequently, a systematic review and meta-analysis of observational studies followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Studies were included if they reported the incidence or risk factors of FI in stroke patients. Subgroup analyses were conducted according to the stage of stroke and survey site. The forest plot showed that the incidence of post-stroke FI was 24.42% (95% confidence interval (CI) = 15.11-33.72). On subgroup analysis, the incidence of FI was 25.73% (95% CI = 14.61-36.86) in the acute stage and 15.99% (95% CI = 9.32-22.67) in the rehabilitation stage. Meanwhile, the incidence of FI in the hospital-based stroke patients was 25.31% (95% CI = 11.37-39.26), which was higher than that in the community-dwelling stroke patients (15.14%, 95% CI = 2.26-28.02). CONCLUSION:The incidence of post-stroke FI is relatively high. Age, gender, cognitive impairment, NIHSS score, antibiotic use, and gavage feeding are closely associated with FI occurrence in stroke patients.

Introduction: Major Depressive Disorder (MDD) is becoming a highly prevalent psychosomatic disease worldwide, posing a serious threat to citizens' health. CNS inflammation is one of the important causes of MDD. Herbal medication Chaihu-Longgu-Muli Decoction (CLM) has antidepressant activity, but the mechanism is still unclear. Methods: This study used CLM as a therapeutic drug and fluoxetine as a positive control to observe its behavioral, pathological, and molecular biological effects on CUMS depression model rats at different dose gradients. Practical LC-MS analysis was used to analyze its main components, and four pathological methods including HE, Nissl, IF, and TEM were used to observe neuropathological changes, polarization typing of microglia, and subcellular changes. WB and PCR were used to observe the molecular levels upstream and downstream of the NLRP3 pathway. Results: The stimulation of CUMS causes inflammatory damage in hippocampus, excessive M1 polarization of microglia, and neuronal pyroptosis. The therapeutic effect of CLM is dose-dependent, and the neuroprotective effect of high-dose CLM is not inferior to that of fluoxetine. CLM promotes M2 polarization of microglia, reduces NLRP3 inflammasome synthesis, downregulates the NLRP3 pathway, thereby preventing neuronal pyroptosis and reducing the release of proinflammatory cytokine. Discussion: CLM can give evidences in antidepression that downregulate the NLRP3 pathway, alleviate hippocampal inflammation and anti-pyroptosis. Further research is needed to verify the in vitro neuroprotective effect and control the inhibition of pyroptosis in enriching its antidepressant mechanism.

Liangxue Tongyu Prescription (LTP) is a classic herbal formula for treating acute intracerebral hemorrhage (AICH) in China. Previous studies have shown that LTP significantly ameliorates neurological impairments and gastrointestinal dysfunction in patients with AICH. However, the underlying molecular mechanism remains unclear. The aim of this study is to investigate whether LTP exerts its neuroprotective effect on AICH rats through the microbiota-gut-brain axis and explore its potential underlying mechanism. In the current study, AICH models were established by injecting autologous whole blood into the right caudate nucleus of rats. Behavioural and pathological evaluations demonstrated that LTP ameliorated neuronal and intestinal damage in AICH rats. Analysis via western blot, quantitative real-time PCR, immunohistochemistry (IHC) and tunel staining indicated that LTP upregulated the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor(NGF) and reduced neuronal cell apoptosis. Additionally, 16S rDNA sequencing revealed that LTP mitigated dysbiosis of intestinal microbiota in AICH rats. LTP increased the levels of noradrenaline (NA), dopamine (DA), glutamate (GLU) and modulated brain-gut peptides such as gastrin (GAS), motilin (MTL), ghrelin in AICH rats. Furthermore, LTP enhanced vagus nerve discharge. In summary, this research provides evidence suggesting that LTP’s influence on AICH may involve modulation of the microbiota-gut-brain axis, offering a potential scientific rationale for its therapeutic efficacy in improving outcomes of AICH.

Inflammatory reactions after acute intracerebral hemorrhage (AICH) contribute significantly to a poor prognosis. Liangxue Tongyu Prescription (LTP) has been proven to be clinically effective in treating AICH. Numerous studies have shown that LTP suppresses brain inflammatory damage in AICH, while the internal mechanisms underlying its action remain unclear. The aim of this study was to verify the anti-inflammatory effects of LTP on an AICH rat model and investigate the potential mechanisms. The AICH rat models were created by injecting autologous blood into the right caudate nucleus. LTP markedly decreased cerebral hematoma and brain water content and recovered from neurological deficits. Meanwhile, LTP prevented microglial activation and reduced the inflammatory reaction caused by pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Notably, the expression of cholecystokinin octapeptide (CCK-8) in the brain and intestine was increased by LTP or CCK-8 treatment. LTP further suppressed nuclear factor kappa B (NF-κB) in the brains of rats with AICH. Moreover, LTP increased the protein and mRNA expression of Occludin and Claudin-1 in the intestine and decreased the levels of lipopolysaccharide (LPS) and diamine oxidase (DAO) in serum. Furthermore, the results showed that LTP increased the protein and mRNA expression of Claudin-5 and zonula occludens-1 (ZO-1) in the brain. CCK-8 receptor antagonists increased the expression of NF-κB and the concentration of pro-inflammatory cytokines. These findings suggested that LTP attenuated neuroinflammation by increasing CCK-8 in the brain and intestine, and its mechanism might be related to alterations in the gut-brain axis (GBA).

Aim: Chaihu-jia-Longgu-Muli-tang (CLM) is derived from “Shang Han Lun” and is traditionally prescribed for treating depression. However, there is still a lack of evidence for its antidepressant effects, and the underlying mechanism is also unclear. This study aimed to assess clinical evidence on the efficacy of CLM in patients with depression using a meta-analysis and to explore its underlying antidepressant molecular mechanisms via network pharmacology.Methods: Eight open databases were searched for randomized controlled trials (RCTs) comparing the effects of CLM alone or combined with serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) in patients with depression, evaluating the total effective rate of the treatment group (CLM alone or combined with SSRIs/SNRIs) and the control group (SNRIs or SSRIs), and comparing changes in depression scale, anxiety scale, sleep scale, inflammation indicators and adverse effects. Subsequently, the active ingredients and target genes of CLM were screened through six databases. Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network and topology analysis were performed. Finally, Molecular docking was applied to evaluate the binding affinity between components and predicted targets.Results: Twenty-four RCTs with a total of 2,382 patients were included. For the efficacy of antidepression and adverse effects, whether CLM alone or in combination with SSRIs/SNRIs, the treatment group has no inferior to that of the control group. Additionally, the intervention of CLM + SSRI significantly improved the symptoms of anxiety and insomnia, and reduced serum IL-6 and TNF-α levels. For network pharmacology, a total of 129 compounds and 416 intersection targets in CLM were retrieved. The interaction pathway between CLM and depression is mainly enriched in PI3K-Akt, JAK-STAT, and NF-κB signaling pathway, PIK3R1, MAPK3, and AKT1 may be the potential targets of Stigmasterol, β-stiosterol, coumestrol.Conclusion: Compared to SSRIs/SNRIs alone, CLM is more effective and safe in treating depression. It not only significantly alleviates depressive mood, but improves symptoms such as anxiety and insomnia, with fewer side effects, especially in combination with SSRI. Its antidepressant mechanism may be correlated with the regulation of the PI3K/Akt signaling pathway and inhibiting inflammatory response.

无菌动物特别是无菌大鼠、小鼠的成功培育技术成为研究微生物与人类生命现象关系的关键技术.严格的无菌动物是指在动物体宿主内外任何部位及生活环境中均检测不出一切生命体.广义的无菌动物还包括清除肠道中大部分菌群的动物,又称为伪无菌动物.目前制作无菌鼠的方法主要有剖腹取胎无菌饲养法制作无菌鼠模型,抗生素鸡尾酒法制作伪无菌鼠模型.本文对无菌鼠模型的制作方法进行总结并对其优缺点进行评价.

目的:观察凉血通瘀方对急性脑出血模型大鼠的神经保护作用,并探索其作用机制.方法:将雄性SD大鼠按随机数字表法分为正常组、假手术组和造模组.造模组采用自体血注入法制作脑出血模型;假手术组以空针置入右侧尾状核,不注血.造模成功的大鼠随机分为模型组和凉血通瘀方组,每组15只;假手术组和正常组每组亦为15只.各组分别灌胃生理盐水或中药,每日1次,连续3?d.模型组与凉血通瘀方组大鼠分别于造模成功后、灌胃3?d后运用Longa五级评分法评价神经功能缺损程度;灌胃3?d后,免疫组化法检测各组5只大鼠脑组织神经生长因子(NGF)表达,蛋白免疫印迹法(Western?Blot)检测各组5只大鼠脑组织脑源性神经营养因子(BDNF)蛋白表达,生化法检测各组10只大鼠脑组织超氧化物歧化酶(SOD)、丙二醛(MDA)含量,酶联免疫吸附测定(ELISA)法检测各组10只大鼠脑组织和肠组织八肽胆囊收缩素(CCK-8)含量.结果:模型组与凉血通瘀方组大鼠灌胃3?d后Longa评分均明显低于造模成功后(P<0.01),灌胃3?d后凉血通瘀方组评分显著低于模型组(P<0.05).与正常组比较,模型组大鼠脑组织NGF平均光密度值、BDNF蛋白表达水平、SOD含量均显著降低(P<0.01),MDA含量显著升高(P<0.01);与模型组比较,凉血通瘀方组大鼠脑组织NGF平均光密度值、BDNF蛋白表达水平、SOD含量均显著升高(P<0.01),MDA含量显著降低(P<0.01).与正常组比较,模型组大鼠脑、肠组织CCK-8含量均显著降低(P<0.01,P<0.05);与模型组比较,凉血通瘀方组大鼠脑、肠组织CCK-8含量均显著升高(P<0.01).结论:凉血通瘀方对急性脑出血模型大鼠具有一定的神经保护作用,其机制可能与增加脑、肠组织CCK-8的含量有关.

目的:通过分析滨海县中医院2020年7月—2022年6月的脑血病患者的预防治疗现状,寻其差距,提出改进措施,提升院医患三方一体的协调共建意识,进一步改善患者的及时就诊率、减少致残率.方法:医院自2021年7月起通过各种宣传教育提高患者的健康管理意识,2020年7月—2021年6月为实施前,2021年7月—2020年6月为实施后,比较实施前后患者的管理效果.结果:实施后患者的病情控制总有效率,显著高于实施前(P＜0.05).实施后患者的血压情况,显著低于实施前(P＜0.05).实施后患者的血脂达标率、血糖达标率、抗血小板应用率等,均显著高于实施前(P＜0.05).结论:脑血管病三级预防尤为重要,做好一级预防,才能远离脑血管病,做好二、三级预防才能改善脑血管病.

Ethnopharmacological relevance: Cerebral infarction is one of the most common types of cerebrovascular diseases that threaten people's health. Compound Tongluo Decoction (CTLD), a traditional Chinese medicine formula, has various pharmacological activities, including the alleviation of cerebral infarction symptoms. Aim of the study: This study aims to explore the potential mechanism by which CTLD alleviates cerebral infarction. Material and methods: Middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation and reperfusion (OGD/R) cell model were established for research. The expression of proteins related to endoplasmic reticulum (ER) stress, ferroptosis, Sonic Hedgehog (SHH) pathway and angiogenesis was analyzed by Western blot analysis. The expression of CD31 was detected by immunofluorescence to investigate angiogenesis. In addition, the expression of GRP78 and XBP-1 in brain tissues was investigated by immunohistochemistry. With the application of Prussian blue staining, iron deposition in brain tissue was detected. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) were detected using ELISA kits. The angiogenesis was analyzed by tube formation assay. Results: The results presented in this research showed that CTLD and 4-phenyl butyric acid (4-PBA; the inhibitor of ER stress) could alleviate cerebral infarction. Mechanistically, CTLD and 4-PBA rescued ER stress and ferroptosis, but promoted SHH signaling in rats with cerebral infarction. In addition, cerebral infarction exhibited a high level of angiogenesis, which was aggravated by CTLD but suppressed by 4-PBA. Furthermore, CTLD inhibited ER stress and ferroptosis, but promoted SHH signaling and angiogenesis in OGD/R-induced PC12 cells, which was partly abolished by SANT-1, an antagonist of SHH signaling. Conclusion: In conclusion, this study revealed that CTLD might inhibit ferroptosis induced by endoplasmic reticulum stress and promote angiogenesis by activating the Sonic Hedgehog pathway in rats with cerebral infarction.

Background. Liangxue Tongyu prescription (LTP) is a commonly used formula for acute intracerebral hemorrhage (AICH) in clinical practice that has significant ameliorative effects on neurological deficits and gastrointestinal dysfunction, yet the mechanism remains elusive. The aim of this study was to investigate the pathway by which LTP alleviates brain damage in AICH rats. Methods. The AICH rat models were established by autologous caudal arterial blood injection. The neurological function scores were evaluated before and after treatment. The water content and the volume of Evans blue staining in the brain were measured to reflect the degree of brain damage. RT-PCR was used to detect the inflammatory factors of the brain. Western blotting was used to detect the expression of the tight junction proteins zonula occludens 1 (ZO-1), occludin (OCLN), and claudin (CLDN) in the brain and colon, followed by mucin 2 (MUC2), secretory immunoglobulin A (SIgA), and G protein-coupled receptor 43 (GPR43) in the colon. Flow cytometry was used to detect the ratios of helper T cells 17 (Th17) and regulatory T cells (Treg) in peripheral blood, and the vagus nerve (VN) discharge signals were collected. Results. LTP reduced the brain damage of the AICH rats. Compared with the model group, LTP significantly improved the permeability of the colonic mucosa, promoted the secretion of MUC2, SigA, and GPR43 in the colon, and regulated the immune balance of peripheral T cells. The AICH rats had significantly faster VN discharge rates and lower amplitudes than normal rats, and these abnormalities were corrected in the LTP and probiotics groups. Conclusion. LTP can effectively reduce the degree of brain damage in AICH rats, and the mechanism may be that it can play a neuroprotective role by regulating the function of the intestinal mucosal barrier.

目的:探究凉血通瘀方对脑出血大鼠肠黏膜屏障的组成结构、选择通透性以及神经功能的影响.方法:将30只SD大鼠随机分为正常组、假手术组、模型组、凉血通瘀组和益生菌组.除正常组和假手术组外,其余各组大鼠通过注射泵控制器注血/二次退针法建立脑出血模型.造模成功后,凉血通瘀组给予凉血通瘀方药液灌胃,益生菌组给予双歧杆菌三联活菌制剂灌胃,每日1次,连续3d.治疗结束后,采用ELISA法检测肠黏膜屏障蛋白Occludin、Claudin-1、ZO-1的表达水平及血清中LPS、DAO、DLA的含量.结果:与模型组比较,凉血通瘀组行为学评分显著下降(P<0.01),益生菌组评分改变不明显(P>0.05).与正常组比较,模型组Occludin、Claudin-1、ZO-1蛋白的表达水平显著降低(P<0.01),血清LPS、DAO、DLA的含量显著增加(P<0.01);凉血通瘀组和益生菌组Claudin-1、ZO-1蛋白的表达水平明显降低(P<0.05),血清LPS、DAO、DLA的含量明显增加(P<0.05).与假手术组比较,模型组Claudin-1、ZO-1蛋白的表达水平显著降低(P<0.01),血清LPS、DAO、DLA的含量显著增加(P<0.01),凉血通瘀组ZO-1蛋白的表达水平明显降低(P<0.05),血清LPS、DAO、DLA的含量显著增加(P<0.01);益生菌组血清LPS的含量显著升高(P<0.01).与模型组比较,凉血通瘀组Claudin-1、ZO-1蛋白的表达水平明显上升(P<0.05),益生菌组Occludin、Claudin-1、ZO-1蛋白的表达水平均显著上升(P<0.01).与模型组比较,凉血通瘀组与益生菌组血清LPS、DAO、DLA的含量显著降低(P<0.01).与凉血通瘀组比较,益生菌组血清DLA的含量显著降低(P<0.01).结论:凉血通瘀方与益生菌制剂均可有效提高肠黏膜屏障紧密连接蛋白Occludin、Claudin-1和ZO-1的表达水平,改善肠黏膜通透性,减少LPS、DAO及DLA等有害物质入血,且益生菌制剂稍优于凉血通瘀方.但在改善脑出血后的神经功能缺损症状方面,凉血通瘀方疗效更为确切.

脑与肠在生理、病理上联系密切,基于"脑肠相通"理论,通腑法是治疗脑病的重要法则,而脑病证候兼夹多变,病机错杂,多采用复合立法,使其相互作用,形成新的功用,增强疗效.根据各病病机的不同,治疗中风、痉证、痫病、痴呆、颤证等,常以通腑法配化痰、滋阴、祛瘀、平肝、清热等法,临床应用时需审证求机,辨证论治.

Purpose: To investigate the protective effects of Compound Tongluo decoction (CTD)on neurological function in rats, and the mechanism involved in its angiogenesis-promoting effect. Methods: Rats were arbitrarily assigned to sham group, permanent middle cerebral artery infarction (pMCAO) group, and PMCAO+CTD group (pMCAO plus 7-day oral treatment with CTD). Neurological deficit scores and volume of stroke-damaged areas were measured after 7 days of treatment. The levels of bone marrow-derived endothelial progenitor cells (BMEPCs) in serum and brain tissues were determined by flow cytometry and immunofluorescence. The expression levels of sonic hedgehog (Shh), vascular endothelial growth factor (VEGF), and angiopoietin-1(Ang-1) at infarct sites and in BMEPCs were quantitated using western blot assay. Results: The results showed that CTD markedly ameliorated neurological deficit, reduced volume of affected areas, and promoted the production and homing of BMEPCs. Moreover, CTD upregulated Shh, VEGF and Ang-1expressions at ischemic sites and EPCs, but promoted the proliferation and metastasis of EPCs. The CTD-induced changes were significantly suppressed by Shh inhibitor cyclopamine (CP). Conclusion: These results demonstrate that CTD promotes angiogenesis after cerebral infarction, probably by stimulating Shh signaling and triggering production and homing of EPCs, thereby providing neuroprotection against cerebral infarction. Thus, CTD is a potential neuroprotective agent against cerebral infarction in humans.

目的:观察中风1号方对急性脑出血(acute intracerebral hemorrhage,AICH)模型大鼠的影响,探讨其初步机制.方法:采用自体尾部血液注入法复制大鼠急性脑出血模型.将大鼠随机分为假手术组、模型组、中风1号方低剂量(6.75 g.kg-1)组和中风1号方高剂量(13.5 g.kg-1)组,连续给予相应的药物灌胃3天.用Longa 5级评分法评估神经功能损伤程度;计算脑组织含水量;检测脑组织伊文思蓝(evans blue,EB)含量,评价血脑屏障通透性;ELISA法检测脑出血周围组织肿瘤坏死因子α(tumor necrosis factor,TNF - α)、白细胞介素1β (interleukin - 1β,IL-1β)水平.结果:与假手术组比较,模型组大鼠24h、72h的Longa5级评分,脑组织含水量,EB含量,TNF-α、IL - 1β水平均升高(P＜0.05,P＜0.01).与模型组比较,中风1号方低剂量可降低模型大鼠神经行为学评分(72 h),脑组织含水量(72 h),EB含量,TNF-α、IL-1β水平(72 h)(P＜0.05,P＜0.01);中风1号方高剂量组可降低模型大鼠的神经行为学评分(72 h),脑组织含水量(72 h),EB含量(24 h、72 h),TNF - α、IL - 1β水平(24 h、72 h)(P＜0.01).结论:中风1号方能改善急性脑出血模型大鼠神经功能损伤,减轻脑水肿,缓解血脑屏障受损,其机制可能与降低脑组织TNF-α、IL-1β水平有关.

目的:探讨凉血通瘀方对脑出血大鼠脑组织TLR4和NF-κB p65的影响.方法:24只SD健康雄性大鼠随机分成正常组、假手术组、模型组和凉血通瘀组,每组6只.模型组和凉血通瘀组采用注射泵控制器注血/二次退针法制作脑出血模型.造模成功后,凉血通瘀组给予凉血通瘀方水剂(1.0 mL/100 g)灌胃,每日1次;假手术组、模型组每日给予等剂量蒸馏水灌胃.各组灌胃3d后进行大鼠行为学评分;Western Blot法测定Toll样受体4(TLR4)、核因子κB(NF-κB p65)蛋白表达变化;RT-PCR法检测脑组织TLR4 mRNA的表达.结果:与正常组比较,模型组、凉血通瘀组大鼠神经学评分升高(P<0.01);与模型组比较,凉血通瘀组大鼠神经学评分降低(P<0.01).与正常组和假手术组比较,模型组大鼠脑组织TLR4、NF-κB p65蛋白表达皆明显升高(P<0.01),凉血通瘀组NF-κB p65蛋白表达升高(P<0.05);与模型组比较,凉血通瘀组大鼠脑组织TLR4蛋白表达明显下降(P<0.01),NF-κB p65蛋白表达下降(P<0.05).模型组大鼠脑组织TLR4 mRNA的表达明显高于正常组、假手术组及凉血通瘀组(P<0.01);凉血通瘀组与正常组、假手术组未见明显差异.结论:凉血通瘀方可改善脑出血大鼠神经功能损伤,抑制脑组织TLR4和NF-κB p65蛋白表达,凉血通瘀方的作用机制可能与调节TLR4/NF-κB p65信号通路,减轻脑炎性损伤有关.

目的 观察定眩颗粒对后循环缺血性眩晕病人血管舒缩因子水平的影响.方法 将240例后循环缺血性眩晕病人随机分为对照组和治疗组,各120例.对照组采用基础治疗加用甲磺酸倍他司汀片,每次6 mg,每日3次;治疗组采用基础治疗加用定眩颗粒,每次1包,每日3次,两组均治疗14 d.比较两组治疗前后眩晕障碍量表(DHI)评分,经颅多普勒(TCD)测定后循环主要血管血流动力学指标变化,质谱分析法检测血清内皮素-1(ET-1)、降钙素基因相关肽(CGRP)含量变化.结果 治疗后,两组DHI评分较治疗前下降,且治疗组DHI评分低于对照组(P<0.05).治疗后,两组双侧椎动脉、基底动脉收缩峰流速较治疗前提高,血管搏动指数较治疗前降低,且治疗组优于对照组(P<0.05).治疗后,两组血清ET-1水平较治疗前降低,CGRP水平较治疗前升高,且治疗组优于对照组(P<0.01).结论 定眩颗粒可能通过干预血管舒缩因子水平,调节后循环血流动力学,提高椎基底动脉系统血流灌注,进而发挥对后循环缺血性眩晕病人的治疗作用.

目的:观察凉血通瘀方对脑出血大鼠行为学评分的影响,并初步探索凉血通瘀方的抗炎作用机制.方法:选取SD大鼠60只,随机分为正常组、假手术组、模型组和凉血通瘀组,每组设定3个时间观察点,分别为用药24 h、72 h、120 h,每个时间点5只大鼠.观察使用凉血通瘀方干预前后,脑出血大鼠行为学评分的变化情况;采用ELISA法检测脑组织TNF-α、IL-1β的表达水平;免疫组织化学检测大鼠脑组织NF-κB的表达水平.结果:1)在72 h时间点,凉血通瘀组行为学评分已明显低于模型组(P<0.05),并持续降低.2)在用药24 h、72 h、120 h 3个时间点,凉血通瘀组的TNF-α、IL-1β均低于模型组(P<0.01).3)在用药24 h、72 h、120 h,凉血通瘀组的NF-κB均低于模型组(P<0.01).结论:凉血通瘀方能够调控脑出血大鼠NF-κB通路活化、抑制炎性因子的分泌,从而减轻炎症反应的发生、降低炎症的级联放大效应,改善了脑出血大鼠的行为学评分,发挥抗炎作用.

目的 探讨益肾复元汤联合胞磷胆碱钠和常规治疗对风火上扰型急性缺血性脑卒中患者的临床疗效.方法 150例患者随机分为对照组和观察组,每组75例,对照组给予胞磷胆碱钠和常规治疗(吸氧、阿司匹林、阿托伐他汀、尿激酶),观察组在对照组基础上加用益肾复元汤,疗程15 d.检测临床疗效、神经功能缺损量表(NIHSS)评分、Barthel指数(BI)评分、改良Rankin量表(mRS)评分、GFAP、SDF-1、S100B、NSE、脑血流灌注指标(PSV、TMV、RI)、不良反应发生率变化.结果 治疗后,2组NIHSS评分、GFAP、S100B、NSE、RI降低(P＜0.05),BI评分、SDF-1、PSV、TMV升高(P＜0.05),以观察组更明显(P＜0.05).治疗3个月后随访,观察组mRS评分低于对照组(P＜0.05).2组不良反应发生率比较,差异无统计学意义(P＞0.05).结论 益肾复元汤联合胞磷胆碱钠和常规治疗可有效改善风火上扰型急性缺血性脑卒中患者脑血流灌注和预后,降低血清GFAP水平,提高血清IGF-1水平,促进神经功能恢复.