参芪益心方对异丙肾上腺素致心肌损伤大鼠IRE1、Cleaved Caspase-3的影响及作用机制研究  

Effects of Shenqi Yixin Formula on IRE1,Cleaved Caspase-3 and Its Mechanism in Rats with Myocardial Injury Induced by Isoproterenol

作　　者：郭继芳 韩宇博[2] 金娟[2] 刘莉[2] GUO Jifang;HAN Yubo;JIN Juan;LIU Li(Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang,China)

机构地区：[1]黑龙江中医药大学,哈尔滨150040 [2]黑龙江中医药大学附属第一医院,哈尔滨150040

出　　处：《中西医结合心脑血管病杂志》2023年第3期432-437,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：黑龙江省省属高等学校基本科研项目(No.2021-KYYWF-0512)。

摘　　要：目的:探讨异丙肾上腺素诱导的心肌损伤及参芪益心方对肌醇需求酶1(IRE1)、裂解凋亡蛋白酶-3(Cleaved Caspase-3)的影响及作用机制研究。方法:将40只SD大鼠随机分为对照组、异丙肾上腺素组、曲美他嗪组、参芪益心方低剂量组和参芪益心方高剂量组。除对照组外,其余各组给予颈背部皮下注射异丙肾上腺素建模,实验连续2周后,对照组给予等量生理盐水,曲美他嗪组给予曲美他嗪混悬液每日5 mg/kg,参芪益心方低剂量组、高剂量组分别给予参芪益心方水煎剂每日10 g/kg、20 g/kg,对照组和异丙肾上腺素组给予等量生理盐水灌胃,实验连续2周。分别在实验给药2周末、4周末进行心电图、超声心动图检查。实验给药4周末苏木精-伊红(HE)染色观察各组心肌组织病理学改变,蛋白免疫印迹法(Western Blot)检测各组心肌组织IRE1、Cleaved Caspase-3蛋白水平。结果:实验4周末,异丙肾上腺素组q波振幅加深、ST段抬高,且较对照组心率明显增快(P<0.05);曲美他嗪组q波振幅减小,参芪益心方低剂量组ST段抬高幅度减小;参芪益心方高剂量组ST段位于等电位线上,无明显偏移,参芪益心方治疗组相比异丙肾上腺素组心率明显降低(P<0.05)。实验4周末,与对照组比较,异丙肾上腺素组大鼠左室前壁舒张末厚度(Dist A)、左室后壁舒张末厚度(Dist C)减小,舒张末心室内径(Dist B)、收缩期心室内径(Dist D)增加,左室射血分数(LVEF)、左心室短轴缩短率(LVFS)明显减低;心肌组织IRE1、Cleaved Caspase-3蛋白表达水平明显升高(P<0.001)。与异丙肾上腺素组比较,各治疗组大鼠在药物干预后各项指标均有改善(P<0.05),且参芪益心方高剂量组优于参芪益心方低剂量组(P<0.05)。与异丙肾上腺素组比较,曲美他嗪组心肌间质少量炎性细胞浸润,心肌纤维轻度肿胀;参芪益心方低剂量组和参芪益心方高剂量组纤维排列相对规则,断裂与空泡变�Objective:To investigate the effects of Shenqi Yixin Formula on isoproterenol(ISO)induced myocardial injury and inositol-requiring enzyme 1(IRE1),Cleaved Caspase-3 and its mechanism.Methods:Forty SD rats were randomly divided into control group,isoproterenol group,trimetazidine group,Shenqi Yixin Formula low-dose group and Shenqi Yixin Formula high-dose group.Except the control group,the other groups were given subcutaneous injection of isoproterenol in the neck and back for modeling,and the control group was given subcutaneous injection of the same amount of normal saline.After 2 weeks of continuous experiment,the control group was given the same amount of normal saline,the trimetazidine group was given trimetazidine suspension 5 mg/kg a day,the Shenqi Yixin Formula low-dose group was given Shenqi Yixin decoction 10 g/kg a day,Shenqi Yixin Formula high-dose group was given Shenqi Yixin decoction 20 g/kg a day,control group and isoproterenol group were given the same amount of normal saline by intragastric administration,the experiment lasted for 2 weeks.Electrocardiogram and echocardiogram were performed at 2 and 4 weeks of experimental administration.Cardiac histopathological changes were observed by hematoxylin-eosin(HE)staining at the end of 4 weeks of administration,and IRE1 and Cleaved Caspase-3 protein levels were detected by Western Blot.Results:At the end of experiment 4 weeks,the q wave amplitude of the isoproterenol group was deepened,the ST segment was elevated and the heart rate of the isoproterenol group was significantly increased compared with that in the control group(P<0.05).Q wave amplitude was decreased in trimetazidine group,and ST segment elevation was decreased in Shenqi Yixin Formula low-dose group.The ST segment of Shenqi Yixin Formula high-dose group was located on the equipotential line,and there was no obvious deviation.Compared with that in isoproterenol group,the heart rate of Shenqi Yixin Formula treatment group was significantly decreased(P<0.05).At the end of experiment 4 weeks,co

关 键 词：心肌损伤 内质网应激 肌醇需求酶1 IRE1 裂解凋亡蛋白酶-3 Cleaved Caspase-3 

分 类 号：R285.5[医药卫生—中药学]