山东中医药大学学报2026，Vol.50Issue(1)：56-67,77,13.DOI:10.16294/j.cnki.1007-659x.2026.01.011
基于AMPK/eNOS信号通路探究钩藤玄参颗粒降低正常高值血压的作用机制
Mechanism of Gouteng Xuanshen Granule(钩藤玄参颗粒)in Reducing Prehypertension Based on AMPK/eNOS Signaling Pathway
摘要
Abstract
Objective:To investigate the mechanisms of Gouteng Xuanshen Granules(钩藤玄参颗粒)on endothelial injury and mitochondrial dysfunction in rats with prehypertension based on the AMPK/eNOS signaling pathway.Methods:In the in vivo experiment,48 SPF-grade WKY rats were randomly divided into six groups:the normal group,model group,positive drug group(Valsartan 8 mg/kg+Atorvastatin 1 mg/kg),and low-,medium-,and high-dose Gouteng Xuanshen Granule groups(1.08,2.16,4.32 g/kg of the granule per day),with eight rats in each group.Except for the normal group,the other groups were subjected to a high-salt and high-fat diet for 8 weeks to induce the model.Following the successful modeling,the experimental groups were given the designated dosage of medicinal solution by gavage for another 8 weeks.Blood pressure was monitored every two weeks for each group.At the end of administration,a biochemical analyzer was used to detect total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),Enzyme-linked immunosorbent assay(ELISA)was employed to determine the serum levels of adenosine triphosphate(ATP),adenosine diphosphate(ADP),and adenosine monophosphate(AMP).Hematoxylin-eosin(HE)staining was performed to observe the pathological changes of the aorta;immunofluorescence was used to detect endothelial cell viability;and Western blot(WB)was applied to analyze the protein expression levels of adenosine monophosphate-activated protein kinase(AMPK),phosphorylated adenosine monophosphate-activated protein kinase(p-AMPK),endothelial nitric oxide synthase(eNOS),and phosphorylated endothelial nitric oxide synthase(p-eNOS).For the in vitro experiment,endothelial cells were divided into the normal group,model group,and medicated serum group of Gouteng Xuanshen Granules.Tetramethylrhodamine methyl ester(TMRM)probe was used to detect the mitochondrial membrane potential of endothelial cells.Dichlorodihydrofluorescein diacetate(DCFH-DA)probe was utilized to measure reactive oxygen species(ROS)in cells.ATP assay kit was adopted to determine the changes of ATP content in endothelial cells.Mito-tracker Green combined with Mito SOX probe was used for the joint detection of mitochondrial ROS in endothelial cells;and WB was performed to detect the protein expression levels of p-AMPK and p-eNOS in endothelial cells.Results:In vivo experimental results showed that compared with the model group,the blood pressure of rats in the Gouteng Xuanshen Granule groups decreased significantly(P＜0.05).In the Gouteng Xuanshen Granule groups,the four blood lipid indexes tended to be normal,the contents of ATP,AMP,and ADP increased(P＜0.05,P＜0.01).HE staining results indicated that the aortic endothelial morphology of rats in the Gouteng Xuanshen Granule groups was restored,and immunofluorescence results showed that endothelial cells in the Gouteng Xuanshen Granule groups were arranged neatly with reduced shedding.In vitro experimental results demonstrated that compared with the model group,the medicated serum group of Gouteng Xuanshen Granules had improved scratch healing ability,increased average fluorescence of membrane potential,decreased ROS and mitochondrial ROS,elevated ATP content,and up-regulated protein expressions of p-AMPK and p-eNOS,with statistically significant differences(P＜0.05,P＜0.01).Conclusion:Gouteng Xuanshen Granules can reduce hypertension caused by endothelial injury by regulating the AMPK/eNOS signaling pathway and improve mitochondrial dysfunction.关键词
钩藤玄参颗粒/正常高值血压/腺苷酸蛋白活化激酶/内皮型一氧化氮酶信号通路/线粒体/内皮损伤Key words
Gouteng Xuanshen Granules(钩藤玄参颗粒)/prehypertension/AMPK/eNOS signaling pathway/mitochondria/endothelial injury分类
医药卫生引用本文复制引用
王婧毅,赵文杰,李博杨,王丹阳,李运伦,齐冬梅..基于AMPK/eNOS信号通路探究钩藤玄参颗粒降低正常高值血压的作用机制[J].山东中医药大学学报,2026,50(1):56-67,77,13.基金项目
国家自然科学基金项目(编号:81974555) （编号:81974555）
