Heart Failure represents the severe stage of various heart diseases. Its global morbidity and mortality are on the rise, making it a serious public health issue that imposes a heavy burden on patients’ families and society. Currently, there are relatively few systematic studies on the changes in specific metabolites and pathways in different stages of heart failure, such as Stage A, Stage B and Stage C. Using untargeted-targeted metabolomics to explore the metabolic characteristics of Heart Failure, and screen out serum metabolic markers with potential diagnostic and prognostic value. This study is a cross-sectional study. A total of 210 heart failure patients from Xiyuan Hospital of China Academy of Chinese Medical Sciences were enrolled between October 2023 and October 2024. Among them, 60 patients were selected for targeted metabolomics analysis via stratified sampling. Serum samples of the patients were collected and pretreated with methanol, then metabolites were detected using untargeted and targeted LC-MS respectively. After the raw data were processed with MSDIAL, pattern recognition was performed using principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). Differential metabolites with variable importance in projection (VIP) > 1 and P < 0.05 were screened, and relevant pathways were analyzed via enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Untargeted metabolomics revealed that, compared with patients in Stages A and B, those with heart failure in Stage C had decreased serum levels of alanine, creatine, and branched-chain amino acids, along with increased levels of citric acid, fumaric acid, and malic acid. The differential metabolites were primarily enriched in pathways including the citric acid cycle, central carbon metabolism, and amino acid metabolism, indicating that energy metabolism plays a crucial role in the occurrence and progression of HF. Targeted metabolomics validated the findings from untargeted metabolomics: compared with Stage A, the level of phosphoenolpyruvate in Stage B was reduced; and in comparison with patients in Stage A or B, patients in Stage C showed decreased serum levels of multiple energy metabolites (e.g., glucose-6-phosphate, fructose-6-phosphate, 3-phosphoglyceric acid, AMP, ADP and ATP) as well as increased levels of malic acid, which is consistent with the characteristics of the “hypermetabolism-energy starvation” paradox. Stage C of heart failure is characterized by energy metabolism collapse (decreased ATP and TCA compensation), and differential metabolites (such as malic acid) may serve as potential candidate biomarkers pending longitudinal validation.

AimBased on metabolomics and proteomics research, we investigate the molecular biological mechanisms underlying vascular cognitive impairment (VCI) in rats induced by hypertension combined with endothelial damage, aiming to identify proteins or metabolites associated with key metabolic pathways.MethodsSPF hypertensive rats (SHR) were used to damage the common carotid artery endothelium with microcurrent to induce vascular cognitive impairment model in rats (Model group), SHR rats (SHR group) and SPF normotensive Wistar-Kyoto rats (WKY) with the same genetic background were used as sham operation groups (no current stimulation after dissection), with 10 rats in each group. Morris water maze, PNT experiment and SPT experiment were used to detect the learning and memory ability of rats. TMT quantitative proteomics technology combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to detect the difference in metabolites and proteins in brain tissue of rats with vascular cognitive impairment.ResultsFrom Day 1-5, compared with the WKY group, both the Model and SHR groups exhibited shortened incubation periods and slower average swimming speeds (P < 0.01); On day 6, compared with the WKY group, the Model group showed a significant decrease in the number of platform crossings (P < 0.05), time spent in the target quadrant (P < 0.05), and total distance traveled in the target quadrant (P < 0.05). Pathological results revealed that, compared with the WKY group, the SHR group and Model group exhibited a decrease in the number of glial cells and neurons in the hippocampal tissue, with relatively loose arrangement of cell bodies and lighter Nissl staining. In the Model group, some hippocampal neurons changed from a granular to a powdery appearance, with nuclear pyknosis, accompanied by cellular edema and necrosis. The metabolomics results showed that there were 437 significantly different metabolites between the Model group and the WKY group, 128 (+) and 309 (-); there were 449 significantly different metabolites between the Model group and the SHR group, 119 (+), 330(-). The differential metabolites in each group were mainly concentrated in metabolic pathways such as alanine, aspartate and glutamate metabolism, arginine and proline metabolism, and amino acid biosynthesis. The proteomics results showed that compared with the WKY group, there were 141 differentially expressed proteins in the Model group, 55 (+), and 86 (-). Pathways with higher connectivity in the action network include "glycine, serine and threonine metabolism", "phenylalanine metabolism", etc.; compared with the SHR group, there were 28 differentially expressed proteins in the Model group and 15 (+). 13 species (-). The significantly enriched pathways are "focal adhesion" and "relaxin signaling pathway".ConclusionRats with hypertension combined with endothelial injury have behavioral disorders, which are similar to the causes and signs of clinical vascular cognitive impairment; the biological mechanisms manifested in the model involve amino acid metabolism disorders, energy metabolism, relaxin signaling pathway and impaired focal adhesion function. Characteristic metabolites in the model group, such as ATP, cAMP, Creatine, Cyanocobalamin, Dopamine, Serotonin, Tryptophan, Uric acid and Vitamin B1 decreased, while GABA, Glucose, Isocitrate and Malate increased.

To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.

There is a lack of in-depth research on the impacts and changes in chronic psychological stress (CPS) on the cardiovascular system after acute myocardial infarction (AMI). This study aims to explore the comorbid mechanism and dynamic evolution of AMI exposed to CPS. 120 Wistar rats were randomly divided into Sham Operation group, Sham Operation + Chronic Unpredictable Mild Stress (CUMS) group, AMI group and AMI + CUMS group, with each group further divided into subgroups at days 7, 14, and 28. The AMI model was created by ligating the left anterior descending coronary artery, and CUMS model was used to induce CPS in rats. Behavioral changes were assessed through open field tests and sucrose preference tests. Cardiac function and structure were evaluated via echocardiography. The serum levels of TNFα, IL-6, NO, ET, CK-MB, cTNT, and ANP were measured using assay kits. Pathological changes in cardiac and brain tissues were observed under an optical microscope. Comparative analysis across different models revealed that CUMS significantly reduced behavioral activities in rats, with an interaction between CUMS and AMI affecting total distance (P < 0.05). Both CUMS and AMI significantly reduced cardiac function indicators, with their interaction effects on LVEF, LVFS, and CO (P < 0.05). AMI significantly altered cardiac structural parameters, particularly on day 28 (P < 0.05); while the impact of CUMS on cardiac structure was not significant, except for a notable reduction in LVAW/s on day 7 in AMI + CUMS group (P < 0.05). AMI caused significant changes in the serum biomarkers, while CUMS only significantly increased cTnT on day 7, ANP, TNFα, and IL-6 on day 14, and CK-MB on day 28, with their interaction effects on the three myocardial injury markers and TNFα (P < 0.05). Comparative analysis across different time points demonstrated that behavioral activity, cardiac function, CK-MB, cTnT, ANP, TNFα, and ET levels decreased significantly over time in the AMI model rats, while the left ventricular mass increased significantly (P < 0.05). Pathologically, compared with stress or AMI alone, the AMI + CUMS group exhibited more severe myocardia cellular degeneration and inflammatory infiltration, causing larger infract areas in myocardial tissue, as well as cell number decreases and morphological changes in hippocampal tissue. AMI with CPS exacerbates myocardial injury through sustained inflammation and endothelial dysfunction, leading to heart-brain pathology manifestations characterized by decreased cardiac function and hippocampal tissue damage.

BackgroundPoor nutritional status may affect outcomes after coronary revascularization, but the association between nutritional status and outcomes in patients undergoing coronary revascularization has not been fully evaluated. This study was based on the MIMIC-IV database to analyze the impact of baseline nutritional status on poor outcomes in patients with coronary revascularization.MethodsPatients with coronary revascularization were screened from the MIMIC-IV database. A geriatric nutritional risk index (GNRI) was calculated and used to divide patients into 4 groups: no malnutrition (Q4: ≥96.79), mild malnutrition (Q3: 90.85–96.78), moderate malnutrition (Q2: 86.37–90.84), and severe malnutrition (Q1: 86.37). The primary outcome measure was 28-day mortality, and the secondary outcome measures were AKI and length of hospital stay. Cox proportional hazards model, Kaplan-Meier survival analysis, restricted cubic spline (RCS), and multiple linear regression model were used for statistical analysis, respectively, to ensure the robustness of study results.ResultsA total of 1,168 patients with coronary revascularization were included. The GNRI demonstrated a significant association with 28-day mortality in patients undergoing coronary revascularization. As a continuous variable, the GNRI exhibited a notable inverse correlation with mortality across unadjusted, partially adjusted, and fully adjusted Cox regression models [hazard ratios (HRs): 0.93, 0.94, 0.96, respectively; all P < 0.001]. When considered as a categorical variable, a low GNRI (first quartile, Q1) was significantly associated with elevated mortality risks (HRs: 2.64, 2.30, 1.82 in the unadjusted, partially adjusted, and fully adjusted models, respectively; all P < 0.05). Subgroup analysis revealed a more pronounced association in patients under 65 years of age (P for interaction = 0.014). Furthermore, reduced GNRI levels were also associated with an increased incidence of AKI and extended hospital lengths of stay.ConclusionGNRI is associated with prognosis in patients with coronary revascularization. Patients with lower GNRI had higher 28-day mortality, greater risk of AKI, and longer hospital stays.

OBJECTIVE:To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS:ApoE-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS:Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION:Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.

Zedoarondiol, a newly discovered compound derived from the roots of zedoary turmeric, a traditional Chinese herb, has demonstrated potential in reducing inflammation of the vascular endothelium and safeguarding it from harm. Nonetheless, the precise mechanism underlying these effects remains to be elucidated. In this study, we established a model of HUVEC injury induced by hydrogen peroxide. We observed whether Zedoarondiol could reduce the adhesion and transendothelial migration (TEM) of inflammatory cells by inhibiting the expression of VCAM-1 and ICAM-1 in HUVECs. The research findings indicate that utilising Zedoarondiol resulted in a significant reduction in the adhesion rate of THP1 cells to HUVECs, leading to a more condensed cytoskeletal structure. Moreover, Zedoarondiol demonstrated a decrease in NF-κBβ-Ser536 phosphorylation levels in H2O2-stimulated human umbilical vein endothelial cells, resulting in a hindered capacity to bind to target genes like ICAM-1 and VCAM-1, This findings may provide a new pharmacological basis and scientific evidence for Zedoarondiol to slow the atherosclerosis progression by maintaining endothelial function.

OBJECTIVE:To discuss the influence of Sailuotong (, SLT) on the Neurovascular Unit (NVUs) of amyloid precursor protein (APP)/presenilin-1(PS1) mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease (AD). METHODS:The mice were allocated into the following nine groups: (a) the C57 Black (C57BL) sham-operated group (control group), (b) ischaemic treatment in C57BL mice (the C57 ischaemic group), (c) the APP/PS1 sham surgery group (APP/PS1 model group), (d) ischaemic treatment in APP/PS1 mice (APP/PS1 ischaemic group), (e) C57BL mice treated with aspirin following ischaemic treatment (C57BL ischaemic + aspirin group), (f) C57BL mice treated with SLT following ischaemic treatment (C57BL ischaemic + SLT group), (g) APP/PS1 mice treated with SLT (APP/PS1 + SLT group), (h) APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment (APP/PS1 ischaemic + donepezil hydrochloride group) and (i) APP/PS1 mice treated with SLT following ischaemic treatment (APP/PS1 ischaemic + SLT group). The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism. The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice. The hippocampus of each mouse was observed by haematoxylin and eosin (HE) and Congo red staining. The ultrastructure of NVUs in each group was observed by electron microscopy, and various biochemical indicators were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression level was detected by Western blot. The mRNA expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS:The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice, which were restored by SLT. The results of HE staining showed that SLT restored the pathological changes of the NVUs. The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex and hippocampus of the APP/PS1 and APP/PS1 ischaemic mice. Furthermore, SLT significantly reduced the content of Aβ, improved the vascular endothelium and repaired the mitochondrial structures. The ELISA detection, western blot detection and qRT-PCR showed that SLT significantly increased the vascular endothelial growth factor (VEGF), angiopoietin and basic fibroblast growth factor, as well as the levels of gene and protein expression of low-density lipoprotein receptor-related protein-1 (LRP-1) and VEGF in brain tissue. CONCLUSIONS:By increasing the expression of VEGF, SLT can promote vascular proliferation, up-regulate the expression of LRP-1, promote the clearance of Aβ and improve the cognitive impairment of APP/PS1 mice. These results confirm that SLT can improve AD by promoting vascular proliferation and Aβ clearance to protect the function of NVUs.

目的 基于核转录因子-κB(NF-κB)信号通路探讨益气活血托毒方对自身免疫性前列腺炎(EAP)小鼠的影响及作用机制.方法 50只C57BL/6小鼠采用前列腺蛋白提纯液联合弗氏完全佐剂制备EAP小鼠模型,将造模成功的40只小鼠随机分为模型组、西药组(坦索罗辛)和中药(益气活血托毒方)低、高剂量组,每组10只,另取10只小鼠作为空白组,各给药组分别予相应药物灌胃,连续4周.观察小鼠一般状况,ELISA检测血清炎症因子及免疫球蛋白含量,HE染色观察前列腺组织病理变化,Western blot检测前列腺组织p-NF-κB p65、p-NF-κB抑制物激酶β(p-IKK-β)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)蛋白表达.结果 与空白组比较,模型组小鼠体质量减少(P＜0.01),血清TNF-α、IL-1β、IgA、IgG、IgM含量升高(P＜0.01,P＜0.05),前列腺组织炎症反应明显,p-NF-κB p65、p-IKK-β、TNF-α、IL-1β蛋白表达升高(P＜0.01,P＜0.05);与模型组比较,中药低、高剂量组和西药组小鼠体质量增加(P＜0.05,P＜0.01),中药高剂量组小鼠血清TNF-α、IL-1β、IgA、IgG、IgM含量明显降低(P＜0.05,P＜0.01),前列腺组织炎症反应明显减轻,p-NF-κB p65、p-IKK-β、TNF-α、IL-1β蛋白表达降低(P＜0.01,P＜0.05).结论 益气活血托毒方可有效改善EAP小鼠前列腺组织病理形态,减轻炎症反应,调节免疫功能,其作用机制可能与抑制NF-κB信号通路相关蛋白p-NF-κB p65、p-IKK-β、TNF-α、IL-1β表达相关.

Dementia has become one of the most important diseases threatening human health. Alzheimer's disease (AD) and vascular dementia (VaD) have the highest incidence rates among the types of dementia, but until now, therapeutic methods have been limited. Panax ginseng has been used in China for thousands of years to treat dementia, and modern medical studies have found that it contains multiple active components, such as ginsenosides, polysaccharides, amino acids, volatile oils and polyacetylenes, many of which have therapeutic effects in treating AD and VaD. Studies have found that ginsenosides have multitarget therapeutic effects in treating dementia, such as regulation of synaptic plasticity and the cholinergic system, inhibition of Aβ aggravation and tau hyperphosphorylation, anti-neuroinflammation, anti-oxidation effects and anti-apoptosis effects. Other active components of Panax ginseng, such as gintonin, oligosaccharides, polysaccharides and ginseng proteins, also have therapeutic effects on AD and VaD. The effectiveness of ginseng-containing Chinese medicine compounds has also been confirmed by clinical and basic investigations in treating AD and VaD. In this review, we summarized the potential therapeutic effects and related mechanisms of Panax ginseng in treating AD and VaD to provide some examples for further studies.

Objective Heart failure with preserved ejection fraction (HFpEF), an increasing public health concern, is increasing in prevalence and is associated with an elevated risk of hospitalization and mortality. Currently, data on the clinical application value of left ventricular global longitudinal strain (LV GLS) in HFpEF are contradictory. Therefore, we performed the following meta-analysis to appraise the diagnostic and prognostic value of LV GLS in HFpEF.Methods PubMed, Medline, Scopus, and Web of Science were retrieved exhaustively from their inception until December 20, 2022, to obtain literature assessing the diagnostic and prognostic value of LV GLS in HFpEF.Results Forty-one studies (including 14,543 patients) published from 2008 to 2022 were included. The results of the meta-analysis were as follows: First, the LV GLS values in HFpEF patients were significantly lower than in healthy individuals (SMD:1.21; 95% CI (0.94, 1.47), p<0.00001, I2=85%; P<0.00001), but substantially higher than in HErEF patients (SMD: -2.03; 95% CI (−2.23, -1.72), p<0.00001, I2=92%; P<0.00001). Second, the pooled diagnostic parameters of LV GLS for HFpEF were as follows: sensitivity, 0.77 (95% CI: 0.71–0.82); specificity, 0.66 (95% CI: 0.58–0.74); DOR, 7.53 (95% CI: 3.19–17.74); AUC for the SROC, 0.81 (95% CI: 0.79–0.87). Finally, the low LV GLS values were correlated with a higher risk of all-cause death (HR: 1.12; 95% CI: 1.01-1.25; p=0.000, I2=84%; P = 0.031) in HFpEF patients.Conclusions LV GLS is impaired in HFpEF patients despite a normal left ventricular ejection fraction, indicating the existence of mild LV contractile dysfunction. Moreover, LV GLS might be an auxiliary indicator for diagnosing HFpEF and predicting all-cause death in HFpEF patients.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementNo### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:N/AI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll relevant data are within the paper.

痴呆属中医学"呆病""善忘"等范畴,中医藏象理论认为,脑为元神之府,由精髓汇聚而成,脑的功能通过五脏来完成,发挥神志记忆的功能,由此可见老年性痴呆的病位虽在脑,但与心肝脾肺肾五脏的关系非常密切,因此,老年性痴呆的防治也符合中医的整体观理论,需要全方位的临床观察和科学评价.

Ethnopharmacological relevance: Ling-Qui-Qi-Hua (LGQH) decoction, composed of Poria cocos (Schw.) Wolf, Cinnamomum cassia (L.) J. Presl, Paeonia veitchii Lynch, and Atractylodes macrocephala Koidz., is a compound formula derived from Ling-Gui-Zhu-Gan decoction recorded in the Treatise on Febrile and Miscellaneous. It has shown cardioprotective effects on patients or rats with heart failure with preserved ejection fraction (HFpEF). Nevertheless, the active ingredients of LGQH and its anti-fibrotic mechanism remain unknown.Aim of the study: To determine the active ingredients in LGQH decoction and verify that LGQH decoction may inhibit left ventricular (LV) myocardial fibrosis in HFpEF rats by blocking the transforming growth factor-81 (TGF-81)/Smads signaling pathway from the perspective of animal experiments.Materials and methods: First, liquid chromatography-mass spectrometry (LC-MS) technology was used to identify active components in the LGQH decoction. Secondly, a rat model of the metabolic syndrome-associated HFpEF phenotype was established and subsequently received LGQH intervention. The mRNA and protein expression of targets in the TGF-81/Smads pathway were detected by quantitative real-time polymerase chain reaction and western blot analysis. Finally, molecular docking was conducted to examine the interactions between the active ingredients in the LGQH decoction and key proteins of the TGF-81/Smads pathways.Results: According to LC-MS analysis, the LGQH decoction contained 13 active ingredients. In animal experiments, LGQH attenuated LV hypertrophy, enlargement, and diastolic function in HEpEF rats. Mechanically, LGQH not only down-regulated TGF-81, Smad2, Smad3, Smad4, a-SMA, Coll I, and Coll III mRNA expressions and TGF-81, Smad2, Smad3, P-Smad2/Smad3, Smad4, a-SMA, and Coll I protein expressions, but also upregulated Smad7 mRNA and protein expressions, which ultimately led to myocardial fibrosis. Furthermore, molecular docking confirmed that 13 active ingredients in the LGQH decoction have excellent binding activities to the critical targets of the TGF-81/Smads pathway.Conclusion: LGQH is a modified herbal formulation with multiple active ingredients. It might alleviate LV remodeling and diastolic dysfunction and inhibit LV myocardial fibrosis by blocking TGF-81/Smads pathways in HFpEF rats.

目的 观察复方芪丹方对高血压和糖尿病致射血分数保留心力衰竭(HFpEF)模型大鼠心脏功能及糖脂代谢的影响.方法 选择SPF级 14 周龄自发性高血压大鼠(SHR),持续高脂高糖饲料喂养 16 周,高脂高糖饲料喂养 2 周后腹腔注射 1%链脲佐菌素(25 mg/kg)复制高血压、糖尿病致HFpEF大鼠模型.将大鼠按随机数字表法分为HFpEF模型组、阳性药物对照组[沙库巴曲缬沙坦钠(诺欣妥)组,给予诺欣妥 18 mg/kg]、复方芪丹方低剂量组(芪丹低剂量组,给予复方芪丹方含生药 4.90 g/kg)、复方芪丹方高剂量组(芪丹高剂量组,给予复方芪丹方含生药 9.80 g/kg);另设SHR模型组(SHR组,给予等体积纯净水)和正常对照组[Wistar-Kyoto(WKY)组,给予等体积纯净水].灌胃 8 周后采用超声评估大鼠心脏功能;心脏超声结束后,腹主动脉取血,分离血浆和血清,检测空腹血糖(FPG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)水平和糖化血清蛋白(GSP)、胰岛素(FINS)、瘦素(LEP)、胰高血糖素(GCG)、C肽,以及血浆心钠素(ANP)和脑钠肽(BNP)水平;同时取心脏组织行苏木素-伊红(HE)染色,光镜下观察心肌组织病理学变化.结果 与WKY组比较,HFpEF模型组舒张早期二尖瓣血流峰值速度(E)、二尖瓣心房收缩期最大血流(A)、E/舒张早期二尖瓣环心肌运动速度(e')比值、ANP、BNP、TC、TG、LDL-C、FPG、GSP、C肽、GCG、LEP、FINS、IRI水平均明显升高,e'、左房射血分数(LAEF)、胰岛素敏感指数(ISI)自然对数(IAI)均明显降低(均P＜0.05);与HFpEF模型组比较,芪丹低、高剂量组E、A、E/e'比值、TC、FPG、C肽、GCG、LEP、FINS、IRI水平均明显降低[E(m/s):0.78±0.13、0.81±0.15 比 1.02±0.15,A(m/s):0.46±0.06、0.43±0.04 比 0.67±0.07,E/e'比值:15.34±4.58、15.01±3.56 比 24.47±6.38,TC(mmol/L):3.16±1.00、2.40±0.69 比 4.61±0.73,FPG(mmol/L):13.92±1.80、12.65±2.13比17.05±3.44,C肽(μg/L):1.84±0.42、1.46±0.42比2.75±0.70,GCG(ng/L):132.79±28.69、122.33±31.47比161.23±21.43,LEP(μg/L):5.77±1.82、5.37±1.02比9.30±1.42,FINS(pmol/L):104.13±27.65、83.57±32.62 比 133.10±32.78,IRI:10.85±3.87、7.73±3.16 比 17.19±5.80,均P＜0.05],e'和IAI明显升高[e'(m/s):5.20±0.52、5.53±0.70 比 4.30±0.62,IAI:-5.45±0.34、-5.07±0.48 比-5.88±0.45,均P＜0.05],芪丹高剂量组LAEF、左室射血分数(LVEF)均显著升高(LAEF:0.52±0.05 比 0.46±0.06,LVEF:0.82±0.05 比 0.75±0.08),ANP、BNP含量和LDL-C水平显著降低[ANP(μg/L):0.48±0.16 比 0.70±0.11,BNP(ng/L):15.87±4.18比21.08±3.23,LDL-C(mmol/L):1.33±0.72比2.47±0.86,均P＜0.05].HE染色显示,复方芪丹方可显著改善心肌细胞形态.结论 复方芪丹方可改善高血压、糖尿病致HFpEF模型大鼠的糖脂代谢,增加胰岛素敏感性,降低心房内压及心室压力,改善心肌病理形态和心脏舒张功能.

目的 通过观察自发性高血压大鼠(SHR)与对照组大鼠血管紧张素(Ang)Ⅱ/核苷酸结合寡聚结构域样受体蛋白(NLRP)3 炎性小体信号通路指标的不同表达,探讨高血压(HTN)对血管老化(VA)影响的可能机制.方法 实验分为Wistar对照组(4 周龄)、SHR模型组(12 周龄)和WKY对照组(12 周龄),体质量180～200 g,正常饲料喂食,持续8 w.尾袖法记录血压;胸主动脉和主动脉弓取材,进行苏木素-伊红(HE)和Masson染色,光镜下观察主动脉病理形态和血管胶原纤维变化;取胸主动脉进行Ca2+/Mg2+ ATP、Na+/K+ ATP的酶活性检测;Western印迹检测各组血管组织AngⅡ、NLRP3、平滑肌(SM)22α、基质金属蛋白酶(MMP)-9、MMP抑制因子(TIMP)-1、质膜Ca2+-ATP 酶(PMCA)3 的蛋白表达.结果 HE和Masson染色显示,Wistar对照组胸主动脉及主动脉弓外膜结构清楚,中膜平滑肌细胞排列规整,内膜较薄;WKY对照组胸主动脉及主动脉弓中膜平滑肌细胞排列尚整齐,各弹力纤维层排列有序,内膜面尚平整;SHR模型组胸主动脉及主动脉弓中膜明显增厚,整体结构凌乱,平滑肌细胞层明显增多,各弹力纤维层增厚扭曲,胶原相对含量增多,内膜面皱缩.与Wistar对照组比较,WKY对照组及SHR模型组主动脉AngⅡ、NLRP3、MMP-9及TIMP-1蛋白表达增多,SM22α蛋白表达降低,差异有统计学意义(P<0.05,P<0.01);与Wistar对照组比较,SHR模型组血压显著升高,主动脉Ca2+/Mg2+ ATP酶活性显著降低(P<0.01).与WKY对照组比较,SHR模型组血压升高,主动脉AngⅡ、NLRP3 蛋白、MMP-9 蛋白表达增多,大鼠主动脉Ca2+/Mg2+ ATP 酶活性及SM22α蛋白表达降低,差异有统计学意义(P<0.05,P<0.01).结论 随着年龄增长,VA程度逐渐加重.HTN可导致血管结构改变,血管重塑,进而影响血管功能,诱发并加剧VA.其机制可能与AngⅡ表达增多,导致NLRP3 炎性小体被激活,诱导血管平滑肌细胞(VSMCs)炎症、迁移、增殖,并进一步导致VSMCs分化标志物SM22α表达的减少,细胞外基质(ECM)MMP-9 增多及调控细胞内Ca2+ 稳态的Ca2+/Mg2+ ATP酶活性降低.

目的 基于趋化活化蛋白因子-1(MCP-1)/Janus激酶2(JAK2)/信号转导和转录激活因子3(STAT3)信号通路探讨理气活血方对球囊损伤糖尿病股动脉慢性下肢缺血大鼠的干预作用.方法 选取清洁级雄性SD大鼠50只,随机取10只作为假手术组,给予普通饲料喂养和血管内导丝穿刺操作,不损伤股动脉;余40只大鼠通过高脂高糖饲料喂食和链脲佐菌素(STZ)腹腔注射方法构建糖尿病模型,然后在糖尿病模型基础上,应用血管内球囊损伤股动脉及髂动脉缩缝方法建立慢性下肢缺血模型.将造模成功大鼠随机分为模型组、辛伐他汀组、理气活血方高剂量组、理气活血方低剂量组,每组10只.辛伐他汀组给予辛伐他汀片1.80 mg/kg灌胃,理气活血方高、低剂量组分别给予理气活血方8.10 g生药/kg和4.05 g生药/kg灌胃,假手术组和模型组给予等容积纯净水灌胃,均1次/d,连续4周.全自动生化分析仪检测血糖、胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,HE染色观察血管病理形态,电镜下观察股动脉内皮的病理形态,Real-time PCR和Western blot法分别检测股动脉中MCP-1、JAK2、STAT3 mRNA和蛋白表达情况.结果 模型组大鼠血糖及血清TC、TG、LDL-C、IL-6、TNF-α水平均明显高于模型组(P均<0.05),辛伐他汀组与理气活血方高、低剂量组大鼠血清TC、TG、IL-6、TNF-α水平均明显低于模型组(P均<0.05).病理观察,模型组大鼠血管内膜增厚,内皮血管平滑肌细胞增生,管腔狭窄,血管内皮拉伤,可见内弹力板、中膜断裂损伤;辛伐他汀组与理气活血方高、低剂量组大鼠内皮血管平滑肌细胞增生减少,管腔狭窄明显减轻,内皮损伤和断裂的内膜部分修复,裸露的内皮有部分覆盖.模型组大鼠股动脉中MCP-1、JAK2、STAT3 mRNA和蛋白相对表达量均明显高于假手术组(P均<0.05);理气活血方高、低剂量组大鼠股动脉中MCP-1、JAK2、STAT3 mRNA和蛋白相对表达量均明显低于模型组(P均<0.05).结论 理气活血方能够改善慢性下肢缺血大鼠的血管功能,机制可能与抑制MCP-1/JAK2/STAT3信号通路,下调炎症因子的表达相关.

目的:系统分析冠心丹参滴丸主要成分及其给药后大鼠体内的主要入血成分.方法:采用高效液相色谱-质谱联用(high performance liquid chromatography-mass spectrometry,LC-MS)方法,分别在正离子模式和负离子模式下对冠心丹参滴丸提取物进行一级和二级质谱分析,通过与对照品及文献比对,确定冠心丹参滴丸的主要成分;在此基础上,采用建立的LC-MS方法分析冠心丹参滴丸给药后的大鼠含药血清,通过与空白大鼠血清比较,确定冠心丹参滴丸的入血成分,并进行结构鉴定.结果:从冠心丹参滴丸提取物中检测到28个主要组分,其中人参皂苷类成分13个、醌类6个(丹参)、酚酸类4个(丹参)和异黄酮类5个(降香).含药血清检测发现,人参皂苷Rb1和Rd、隐丹参酮和丹参酮ⅡA为冠心丹参滴丸给药后在大鼠体内的主要入血成分.结论:人参皂苷类和丹参中醌类成分是冠心丹参滴丸的主要成分和入血的主要成分,该研究为冠心丹参滴丸后期的药效物质基础和质量控制研究奠定基础.

目的 观察高脂、高盐、高糖饲料等多种危险因素结合高血压大鼠(SHR)造成认知障碍复合模型大鼠的脑组织病理形态和铁沉积的变化.方法 14周龄SPF级大鼠,每组8只,正常对照组(同遗传背景WKY大鼠,WKY组),SHR大鼠随机分4组:对照组(SHRs组)、高脂组(HFAT-SHRs组)、高盐组(HSAIL-SHRs组)、高糖-脂组(DM-SHRs组,同时给予1％的链脲佐菌素腹腔注射,以血糖含量检测在11.1 mmol/L以上作为糖尿病模型标准),WKY组和SHRs组予普通饲料,模型组分别予高脂、高盐和高糖饲料,干预32周.检测大鼠血清及脑组织铁含量的变化、光镜下观察大鼠脑组织病理形态和亚铁含量(普鲁士蓝染色)变化,ELISA法检测大鼠炎症因子水平、胆碱能水平和β-AP的含量.结果 与WKY组比较,各模型组大鼠脑组织存在细胞排列紊乱,细胞核固缩,尼氏小体减少或消失的情况,铁染色显示铁的面积增加,以DM-SHRs组更为显著;SHRs组与3个模型组大鼠乙酰胆碱(ACh)、乙酰胆碱酯酶(AChE)水平降低,白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平升高(P＜0.05,P＜0.05),血清和脑组织铁含量不同程度增加(P＜0.05,P＜0.05),组间比较无统计学意义(P＞0.05).结论 高脂、高盐和高糖因素能改变脑细胞组织形态,促使铁沉积,抑制内源性抗氧化活性,铁含量超载是高血压脑损害中导致认知障碍的可能因素之一.