益心泰对慢性心力衰竭大鼠线粒体分裂蛋白Fis1、Mff的影响  

Effect of Yixintai on Mitochondrial Fission Proteins Fis1 and Mff in Rat Model of Chronic Heart Failure

作　　者：刘承鑫 魏佳明 王子焱 施敏 袁惠 唐云 李雅 郭志华 LIU Chengxin;WEI Jiaming;WANG Ziyan;SHI Min;YUAN Hui;TANG Yun;LI Ya;GUO Zhihua(First Clinical College of Chinese Medicine,School of Traditional Chinese Medicine(TCM),School of Pharmacy,Hunan Key Laboratory of Colleges and Universities of Intelligent TCM Diagnosis and Preventive Treatment of Chronic Diseases,Internet+TCM Diagnosis and Treatment of Chronic Diseases and Intelligent Application of Health Care Joint Postgraduate Training Base,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学第一中医临床学院,中医学院,药学院,慢病中医智能诊断与治未病湖南省普通高等学校重点实验室,互联网+慢病中医诊治与养生智能化应用研究生联合培养基地,长沙410208

出　　处：《中国实验方剂学杂志》2024年第4期143-151,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(82174343);湖南省自然科学基金项目(2021JJ30495);湖南省卫生健康委科研计划项目(D202303017861);湖南省研究生科研创新项目(CX20220808);湖南省中医药科研计划项目(2021064,A2023017);湖南中医药大学“一方”研究生创新项目(2023YF10)。

摘　　要：目的:研究益心泰对慢性心力衰竭大鼠线粒体分裂蛋白的干预作用及其机制。方法:60只SD大鼠随机抽取10只作为假手术组,剩余50只采用结扎左冠状动脉前降支法制备心肌梗死后心力衰竭大鼠模型。将造模成功的大鼠随机分为模型组、益心泰低、中、高剂量组(1.4、2.8、5.6 g·kg^(-1))、曲美他嗪组(10 mg·kg^(-1)),各给药组予相应剂量药物灌胃,模型组和假手术组给予等体积的生理盐水灌胃,连续给药28 d。采用酶联免疫吸附测定法(ELISA)检测大鼠血清氨基末端B型利钠肽(NT-pro BNP)、B型利钠肽(BNP)、腺嘌呤核苷三磷酸(ATP)含量;彩色多普勒超声成像仪检测心功能指标;苏木素-伊红(HE)染色、马松(Masson)染色法观察心脏病理形态学改变,使用Image J软件计算胶原容积分数(CVF);透射电镜观察心肌细胞超微结构变化;原位末端标记法(TUNEL)染色检测心肌组织细胞凋亡率;蛋白免疫印迹法(Western blot)检测心肌组织线粒体外膜线粒体分裂蛋白1(Fis1)、线粒体分裂因子(Mff)表达。结果:与假手术组比较,模型组血清NT-pro BNP、BNP含量显著升高(P<0.01),ATP含量显著降低(P<0.01),左心室射血分数(LVEF)及左心室短轴缩短率(LVFS)下降(P<0.01),左室舒张末期内径(LVIDd)、左室收缩末期内径(LVIDs)升高(P<0.01),心肌细胞排列紊乱、炎性细胞浸润、胶原纤维增多、CVF上升(P<0.01),心肌及线粒体出现损伤,心肌细胞凋亡指数升高(P<0.01),心肌组织线粒体分裂蛋白Fis1、Mff表达上调(P<0.01);与模型组比较,益心泰低、中、高剂量组及曲美他嗪组血清NT-pro BNP、BNP含量降低(P<0.05),ATP含量升高(P<0.05),益心泰低、中、高剂量组及曲美他嗪组LVEF、LVFS升高(P<0.01),LVIDd、LVIDs均降低(P<0.01),各剂量益心泰治疗组及曲美他嗪组心肌炎症损伤减轻、纤维化得到改善,CVF降低(P<0.01),各剂量益心泰治疗组及曲美他嗪组心肌线粒体结构得到改善,各剂�Objective:To study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure.Method:Ten of 60 SD rats were randomly selected as the sham operation group,and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction.The successfully modeled rats were randomized into model,low-,medium-,and high-dose(1.4,2.8,and 5.6 g·kg^(-1),respectively)Yixintai,and trimetazidine(10 mg·kg^(-1))groups.The rats were administrated with corresponding doses of drugs by gavage,and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days.Enzyme-linked immunosorbent assay(ELISA)was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide(NT-pro BNP),B-type natriuretic peptide(BNP),and adenosine triphosphate(ATP)in the serum.Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators.Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart,and Image J was used to calculate collagen volume fraction(CVF).Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells.Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL)was employed to measure the apoptosis rate of myocardial cells.Western blot was employed to determine the protein levels of mitochondrial fission protein 1(Fis1)and mitochondrial fission factor(Mff)in the outer mitochondrial membrane of the myocardial tissue.Result:Compared with the sham operation group,the model group showed elevated levels of NT-pro BNP and BNP in the serum,decreased ATP content,left ventricular ejection fraction(LVEF),and left ventricular fraction shortening(LVFS),increased left ventricular end-diastolic diameter(LVIDd)and left ventricular end-systolic diameter(LVIDs),disarrangement of myocardial cells,inflammat

关 键 词：益心泰 心力衰竭 线粒体动力学 凋亡 线粒体分裂 

分 类 号：R2-0[医药卫生—中医学] R33R289R541.61