黄芪生脉饮对疲劳合并心肌损伤大鼠模型的作用及相关机制  

Effect and mechanism of Huangqi Shengmai Decoction in treatment of joint rat model of fatigue and myocardial injury

作　　者：袁亚慧 袁蓉[1,2] 缪宇 王娅[1,2] 李芃琪 惠稼祺 潘予璠 李梓涵 信琪琪 丛伟红 YUAN Ya-hui;YUAN Rong;MIAO Yu;WANG Ya;LI Peng-qi;HUI Jia-qi;PAN Yu-fan;LI Zi-han;XIN Qi-qi;CONG Wei-hong(Laboratory of Cardiovascular Diseases,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;National Clinical Research Center for Chinese Medicine Cardiology,Beijing 100091,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]中国中医科学院西苑医院心血管病实验室,北京100091 [2]国家(中医)心血管病临床医学研究中心,北京100091 [3]天津中医药大学,天津301617

出　　处：《中国中药杂志》2022年第19期5292-5298,共7页China Journal of Chinese Materia Medica

基　　金：中国中医科学院科技创新工程项目(CI2021A00914);中医药传承与创新“百千万”人才第四批全国中医(西学中)优秀人才研修项目(国中医药人教发[2019]13号);国家自然科学基金项目(82004193);浙江省中西医结合循环系疾病诊治重点实验室开放基金项目(2C32006)。

摘　　要：探讨黄芪生脉饮对疲劳合并心肌损伤模型大鼠的心脏保护作用及相关机制.Wistar大鼠分为假手术组、模型组、盐酸地尔硫[艹卓]组及黄芪生脉饮组.模型组及给药组大鼠力竭游泳14 d后,进行冠状动脉左前降支高位结扎手术.假手术组不游泳、心脏手术仅穿线不结扎.自术后第4天起,模型组及给药组继续游泳4周,同时盐酸地尔硫[艹卓]组灌胃给予盐酸地尔硫[艹卓]20 mg·kg^(-1)·d^(-1),黄芪生脉饮组灌胃给予黄芪生脉饮浸膏0.95 g·kg^(-1)·d^(-1),假手术组、模型组灌胃给予等体积生理盐水,共给药4周.通过检测左心室射血分数(left ventricular ejection fractions,LVEF)、左心室短轴缩短率(left ventricular fractional shorte-ning,LVFS)、抓力、心脏病理形态学等指标,探讨黄芪生脉饮抗疲劳及心脏保护的作用;Western blot检测心肌组织磷酸酶及张力蛋白同源物诱导的蛋白激酶1(PTEN-induced putative kinase 1,PINK1)、Parkin蛋白表达水平,初步阐明黄芪生脉饮通过抑制线粒体自噬改善心肌损伤的机制.结果显示,与假手术组比较,模型组心功能指标LVEF、LVFS显著下降(P<0.01),抓力下降(P<0.05),血清尿素氮(urea nitrogen,BUN)、醛固酮(aldosterone,ALD)水平显著升高(P<0.01),心肌结缔组织增生、纤维化比例显著增加(P<0.01),心肌组织PINK1、Parkin蛋白表达水平显著升高(P<0.01).与模型组相比,黄芪生脉饮干预4周可显著提高大鼠LVEF和LVFS(P<0.01)、显著提高抓力(P<0.01)、降低血清BUN(P<O.01)及ALD水平(P<0.05)、减轻心肌的病理损伤和纤维化程度(P<0.01);同时黄芪生脉饮组大鼠心肌组织PINK1(P<0.01)和Parkin(P<0.05)蛋白表达水平显著降低,提示黄芪生脉饮对疲劳合并心肌损伤有明确的保护作用,其机制可能与抑制线粒体过度自噬、抑制过高的ALD水平从而改善心肌纤维化、保护心肌有关.This study aims to investigate the effects and the underlying mechanism of Huangqi Shengmai Decoction(HQSMD)in the treatment of fatigue and myocardial injury in a joint rat model.Wistar rats were assigned into 4 groups:sham,model,diltiazem hydrochloride(positive control),and HQSMD.The joint model of fatigue and myocardial injury was established by 14-day exhausted swimming followed by high ligation of the left anterior descending coronary artery.The rats in the sham group underwent a sham operation without coronary artery ligation or swimming.Since the fourth day after the ligation,swimming was continued in the model group and the drug-treated groups for the following 4 weeks.Meanwhile,the rats in the positive control group and the HQSMD group were respectively administrated intragastrically with diltiazem hydrochloride(20 mg·kg^(-1)·d^(-1))and HQSMD(0.95 g·kg^(-1)·d^(-1))for 4 weeks,while the shams and the models were given the same volume of normal saline.The left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),grip strength,and myocardial pathophysiological changes were measured to evaluate the anti-fatigue and cardioprotective effects of HQSMD.The protein levels of PTEN-induced putative kinase 1(PINK1)and parkin in the myocardium were measured by Western blot to preliminarily elucidate the mechanism of HQSMD in ameliorating myocardial injury by suppressing mitochondrial autophagy.Compared with the shams,the models showed weakened heart function(LVEF and LVFS,P<0.01),decreased grasping ability(P<0.05),elevated blood urea nitrogen(BUN)and aldosterone(ALD)levels(P<0.01),aggravated myocardial fibrosis and connective tissue hyperplasia(P<0.01),and up-regulated protein levels of PINK1(P<0.01)and parkin(P<0.05).Four-week treatment with HQSMD increased the LVEF and LVFS levels(P<0.01),enhanced the grip strength(P<0.01),reduced the serum levels of BUN(P<0.01)and ALD(P<0.05),alleviated the pathological injury and fibrosis in the myocardium(P<0.01),and down-regulated the protein leve

关 键 词：黄芪生脉饮 疲劳 心肌损伤 线粒体 自噬 

分 类 号：R285.5[医药卫生—中药学]