摘要
目的探讨芪丹利心丸防治心肌梗死后心肌纤维化的可能作用机制。方法采用左冠状动脉结扎术建立心肌梗死大鼠模型,随机分为模型组、卡托普利组和芪丹利心丸组,另设假手术组只穿线不结扎,每组10只。术后第2天,芪丹利心丸组给予芪丹利心丸2.43 g/(kg·d)灌胃,卡托普利组给予卡托普利片2.25 mg/(kg·d)灌胃,假手术组和模型组给予去离子水10 ml/(kg·d)灌胃。4周后检测各组心脏血流动力学指标[包括心率(HR)、左心室收缩压(LVSP)、左心室舒张末压(LVEDP)、左心室内压最大上升速率(+dp/dt max)、左心室内压最大下降速率(-dp/dt max)],称取左心室重量(LVM)并计算左心室质量指数(LVMI),HE染色进行病理学观察,Masson染色计算胶原容积分数(CVF),检测左心室心肌组织miR-133a、转化生长因子β1(TGF-β1)和结缔组织生长因子(CTGF)mRNA及TGF-β1、CTGF蛋白表达情况。结果与假手术组比较,模型组LVSP、+dp/dt max,-dp/dt max下降,LVEDP升高,LVMI、CVF增大,miR-133a下调,TGF-β1和CTGF蛋白及mRNA表达增多(P<0.01)。与模型组比较,芪丹利心丸组LVSP、+dp/dt max,-dp/dt max上升,LVEDP降低,LVMI、CVF减小,miR-133a上调,TGF-β1和CTGF蛋白及mRNA表达减少(P<0.05或P<0.01)。HE染色显示,模型组见梗死边缘区残存的心肌纤维混乱、部分断裂,肌间隙增宽明显,而卡托普利组和芪丹利心丸组心肌梗死边缘区心肌纤维走形相对规整,多数胞膜基本完整。结论芪丹利心丸可防治心肌梗死大鼠心肌纤维化,其机制可能与miR-133a/TGF-β1/CTGF信号通路有关。
Objective To investigate the possible mechanism of Qidan Lixin Pill（ 芪丹利心丸） in prevention and treatment of myocardial fibrosis after myocardial infarction. Methods Rat models of myocardial infarction were established by permanent left coronary artery ligation and were randomly divided into model group,captopril group and Qidan Lixin Pill group,and a sham-operation group was threaded without ligating,with 10 rats in each group. On the second day after surgery rats were administered intragastrically for 4 weeks,and Qidan Lixin Pill group was given Qidan Lixin Pill 2. 43 g/（ kg · d）,captopril group given captopril tablet 2. 25 mg/（ kg · d）,and the other groups given 10 ml/（ kg·d） of deionized water for intragastric administration. After 4 weeks,the cardiac hemodynamics indicators including heart rate（ HR）,left ventricular systolic pressure（ LVSP）,left ventricular end-diastolic pressure（ LVEDP）,maximum rate of increase in left ventricular pressure（ ＋ dp/dt max）,maximum rate of decrease in left ventricular pressure（-dp/dt max） were detected. The left ventricular mass（ LVM） was weighed,the left ventricular mass index（ LVMI） calculated,and HE staining was used for pathological observation while Masson staining was used to calculate collagen volume fraction（ CVF）. The miR-133 a,the expressions of mRNA and protein of transforming growth factor-β1（ TGF-β1） and connective tissue growth factor（ CTGF） in each group were detected.Results Compared with sham-operation group,the LVSP and ＋ dp/dt max,-dp/dt max in model group were decreased while LVEDP was increased,LVMI and CVF increased,miR-133 a decreased,and the expressions of mRNA and TGF-β1 and CTGF protein were increased（ P〈0. 01）. Compared with the model group,the LVSP and ＋ dp/dt max,-dp/dt max in Qidan Lixin Pill group were increased while LVEDP was decreased,LVMI and CVF decreased,miR-133 a increased,and the expressions of mRNA and TGF-β1 and CTGF protein were decreased（ P〈0. 05 or
作者
陈慧洋
娄利霞
赵一舟
李春红
黄涯
张冬梅
王帅
侯雅竹
吴爱明
商洪才
CHEN Huiyang;LOU Lixia;ZHAO Yizhou;LI Chunhong;HUANG Ya;ZHANG Dongmei;WANG Shuai;HOU Yazhu;WU Aiming;SHANG Hongcai(Dongzhimen Hospital,Beijing University of Chinese Medicine,Key Laboratory of Chinese Internal Medicine by Ministry of Education and Beijing,Beijing,100700;First Teaching Hospital of Tianjin University of Traditional Chinese Medicine)
出处
《中医杂志》
CSCD
北大核心
2018年第20期1771-1776,共6页
Journal of Traditional Chinese Medicine
基金
国家中医药管理局国家中医临床研究基地业务建设科研专项课题(JDZX2015008)
