黄芪总皂苷对心衰大鼠心肌细胞凋亡和线粒体膜电位的影响

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (9): 1218-1223.

黄芪总皂苷对心衰大鼠心肌细胞凋亡和线粒体膜电位的影响

尤旭^*, 朱小芳, 胡运鹏, 龚杨, 赵磊

荆州市中心医院院前急救科, 湖北荆州 434000

收稿日期:2019-06-13 修回日期:2019-11-14 出版日期:2020-09-05 发布日期:2020-09-04
通讯作者: ^*2416325802@qq.com
基金资助:
2017—2018年度湖北省卫生计生委面上项目(WJ2017M242)

Effects of total astragalosides on cardiomyocyte apoptosis and mitochondrial membrane potential in rats with heart failure

YOU Xu^*, ZHU Xiao-fang, HU Yun-peng, GONG Yang, ZHAO Lei

Pre-hospital Emergency Department, Jingzhou Central Hospital, Jingzhou 434000, China

Received:2019-06-13 Revised:2019-11-14 Online:2020-09-05 Published:2020-09-04
Contact: ^*2416325802@qq.com

摘要/Abstract

摘要： 目的研究黄芪总皂苷(ASTs)对心衰大鼠心肌细胞凋亡和线粒体膜电位的影响和机制。方法将大鼠分成对照组(normal)、心衰组(model)、AST低、中、高剂量干预组(10、20、40 mg/kg灌胃),每组12只,检测大鼠心功能指标。取大鼠心肌组织,TUNEL法检测细胞凋亡;黄嘌呤氧化酶法检测SOD活性;二硫代二硝基甲基苯法检测GSH-PX活性;硫代巴比妥酸法检测MDA含量;JC-1法检测线粒体膜电位;Western blot检测c-caspase-3、c-caspase-9、p-AKT、p-p38MAPK蛋白和线粒体、胞质中cyt-c蛋白表达水平。结果与对照组比较,model组大鼠LVSP、+dp/dt_max和-dp/dt_max降低(P＜0.05);细胞凋亡率和c-caspase-3、c-caspase-9蛋白水平升高(P＜0.05);SOD、GSH-PX活性降低(P＜0.05);MDA含量升高(P＜0.05);线粒体膜电位降低(P＜0.05);线粒体中cyt-c蛋白水平降低(P＜0.05);胞质中cyt-c蛋白水平升高(P＜0.05);p-AKT水平降低(P＜0.05);p-p38MAPK水平升高(P＜0.05)。与心衰组比较,AST-L、AST-M、AST-H组大鼠LVSP、+dp/dt_max和-dp/dt_max升高;细胞凋亡率和c-caspase-3、c-caspase-9蛋白水平降低;SOD、GSH-PX活性升高;MDA含量降低;线粒体膜电位升高;线粒体中cyt-c蛋白水平升高;胞质中cyt-c蛋白水平降低;p-AKT水平升高;p-p38MAPK水平降低;并且黄芪总皂苷作用浓度越大,对心衰大鼠模型影响也越大。结论黄芪总皂苷抑制心衰大鼠心肌细胞凋亡,其作用机制可能与提高线粒体膜电位和影响AKT、p38MAPK信号通路有关。

关键词: 心衰大鼠, 心肌细胞凋亡, 线粒体膜电位, 氧化损伤, 黄芪总皂苷

Abstract: Objective To study the effect and mechanism of total astragalosides(ASTs) on myocardial cell apoptosis and mitochondrial membrane potential in rats with heart failure. Methods Rats were divided into control group(normal), heart failure group(model), AST low, medium and high intervention group (10, 20 and 40 mg/kg intragastric administration) and 12 rats in each group. Cardiac function was measured in rats. Myocardial tissue was taken from rats, apoptosis was detected by TUNEL assay, the activity of SOD was detected by xanthine oxidze method, the activity of GSH-PX was determined by dithio-dinitromethylbenzene method, MDA content was determined by thiobarbituric acid method, the mitochondrial membrane potential was measured by JC-1 method. Western blot was used to detect the expression levels of c-caspase-3, c-caspase-9, p-AKT, p-p38MAPK and Cyt-C in mitochondria and cytoplasm. Results Compared with normal group, LVSP,+dp/dt_max,-dp/dt_max in model group decreased(P＜0.05),the apoptotic rate and the level of c-caspase-3 and c-caspase-9 protein increased(P＜0.05), the activities of SOD and GSH-PX decreased(P＜0.05), the content of MDA increased(P＜0.05), the mitochondrial membrane potential decreased(P＜0.05), the level of Cyt-C protein in mitochondria decreased(P＜0.05), Cyt-c protein level in cytoplasm increased(P＜0.05), the level of p-AKT decreased, the level of p-p38MAPK increased(P＜0.05). Compared with model group, LVSP, +dp/dt_max,-dp/dt_max increased in AST-L, AST-M and AST-H groups, the apoptotic rate and c-caspase-3,c-caspase-9 protein levels decreased, the activities of SOD and GSH-PX increased, the content of MDA decreased, the mitochondrial membrane potential increased, the level of Cyt-C protein in mitochondria increased, Cyt-c protein level in cytoplasm decreased, the level of p-AKT increased, the level of p-p38 MAPK decreased, the higher the concentration of total astragalosides is, the greater the effect on heart failure rat model. Conclusions Total astragalosides inhibit cardiomyocyte apoptosis in rats with heart failure. The mechanism may be related to the increase of mitochondrial membrane potential and the influence of AKT and p38MAPK signaling pathways.

Key words: rats with heart failure, cardiomyocyte apoptosis, mitochondrial membrane potential, oxidative damage, total astragalosides

中图分类号:

R966

尤旭, 朱小芳, 胡运鹏, 龚杨, 赵磊. 黄芪总皂苷对心衰大鼠心肌细胞凋亡和线粒体膜电位的影响[J]. 基础医学与临床, 2020, 40(9): 1218-1223.

YOU Xu, ZHU Xiao-fang, HU Yun-peng, GONG Yang, ZHAO Lei. Effects of total astragalosides on cardiomyocyte apoptosis and mitochondrial membrane potential in rats with heart failure[J]. Basic & Clinical Medicine, 2020, 40(9): 1218-1223.

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