乌头赤石脂丸方对急性心肌梗死后心肌肥厚模型大鼠心肌组织氧化应激及Keap1/Nrf2/HO-1/NQO-1通路的影响  

Effects of Wutou Chishizhi Pill(乌头赤石脂丸)on Myocardial Oxidative Stress and Keap1/Nrf2/HO-1/NQO-1 Pathway in Myocardial Hypertrophy Model Rats after Acute Myocardial Infarction

作　　者：王鑫赫 史晓梅 肖钰雪 王松 谢璐璐 郭军鹏[1] 刘宏岩[1] WANG Xinhe;SHI Xiaomei;XIAO Yuxue;WANG Song;XIE Lulu;GUO Junpeng;LIU Hongyan(Changchun University of Chinese Medicine,Changchun,130117)

机构地区：[1]长春中医药大学,130117

出　　处：《中医杂志》2023年第10期1036-1043,共8页Journal of Traditional Chinese Medicine

基　　金：吉林省科技厅科技发展计划项目(20170101007JC)。

摘　　要：目的 探讨乌头赤石脂丸方治疗急性心肌梗死后心肌肥厚的可能作用机制。方法 将40只SD大鼠随机分为正常组、模型组、培哚普利叔丁胺组和乌头赤石脂丸组,每组10只。除正常组外,其余3组通过结扎左冠状动脉前降支制备急性心肌梗死,术后各组大鼠正常饲养28天后建立心肌梗死后心肌肥厚模型。造模成功后培哚普利叔丁胺组给予培哚普利叔丁胺片0.4 mg/(kg·d)灌胃,乌头赤石脂丸组给予乌头赤石脂丸药液4.9 g/(kg·d)灌胃,正常组和模型组给予6.67 ml/(kg·d)生理盐水灌胃,均干预28天。观察各组大鼠心肌肥厚指数(包括心脏质量指数和左心室质量指数);HE染色、Masson染色法观察心肌细胞病理学变化;检测血清中心房钠尿肽(ANP)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)和羟脯氨酸(HYP)含量,心肌组织中超氧化物歧化酶(SOD)、丙二醛(MDA)和活性氧(ROS)水平,检测心肌组织中Kelch样环氧氯丙烷相关蛋白-1 (Keap1)、核因子E2相关因子2 (Nrf2)、血红素氧合酶-1 (HO-1)、醌氧化还原酶-1(NQO-1)、B细胞淋巴瘤-2 (Bcl-2)和Bcl-2相关X蛋白(Bax)蛋白表达水平。结果 与正常组比较,模型组大鼠心脏质量指数和左心室质量指数显著升高(P<0.01),病理结果显示心肌细胞横截面积变大,心肌纤维紊乱,心肌组织周围胶原纤维断裂、紊乱;血清ANP、AngⅡ、ALD、HYP含量均显著升高,心肌组织中MDA、ROS水平及Keap1、Bax蛋白表达升高,SOD活性及Nrf2、HO-1、NQO-1、Bcl-2蛋白表达降低(P<0.05或P<0.01)。与模型组比较,乌头赤石脂丸组和培哚普利叔丁胺组大鼠心脏质量指数和左心室质量指数降低(P<0.01),心肌病理损伤改善,心肌细胞横截面积明显减小,血清中AngⅡ、ALD、ANP、HYP含量及心肌组织MDA、ROS水平及Keap1、Bax蛋白表达显著降低,SOD活性及Nrf2、HO-1、NQO-1、Bcl-2蛋白表达显著升高(P<0.05或P<0.01)。乌头赤石脂丸组在降低心脏质量指数和左心Objective To explore the possible mechanism of Wutou Chishizhi Pill(乌头赤石脂丸,WCP)in treating myocardial hypertrophy after acute myocardial infarction(AMI).Methods Forty SD rats were randomly divided into normal group,model group,perindopril tert-butylamine group and WCP group,with 10 rats in each group.Except for the normal group,AMI model was prepared by ligation of the left anterior descending coronary artery;rats in each group were fed normally for 28 days after operation to establish the model of myocardial hypertrophy after AMI.After successful modeling,the perindopril tert-butylamine group was given 0.4 mg/(kg·d)of perindopril tert-butylamine tablets,while the WCP group was given 4.9 g/(kg·d)of WCP liquid,and the normal group and the model group were given 6.67 ml/(kg·d)of normal saline,all by gavage for 28 days.The myocardial hypertrophy indexes including heart mass index and left ventricular mass index were assessed.HE staining and Masson staining were used to observe the pathological changes of cardiomyocytes.The serum atrial natriuretic peptide(ANP),angiotensinⅡ(AngⅡ),aldosterone(ALD)and hydroxyproline(HYP)levels were detected,as well as the superoxide dismutase(SOD),malondialdehyde(MDA)and reactive oxygen species(ROS)levels in myocardial tissue.The protein expression levels of Kelch-like epichlorohydrin-related protein-1(Keap1),nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),quinone oxidoreductase-1(NQO-1),B-cell lymphoma-2(Bcl-2)and Bcl-2-related X protein(Bax)in myocardial tissue were detected.Results Compared to those in the normal group,the heart mass index and left ventricular mass index of rats in the model group significantly increased(P<0.01),and the pathological results showed that the cross-sectional area of cardiomyocytes became larger,with disordered myocardial fibers,and broken and disordered collagen fibers around the myocardial tissue;serum ANP,AngⅡ,ALD,and HYP levels significantly increased,as well as the MDA and ROS levels in myocardial tissue and Kea

关 键 词：急性心肌梗死 心肌肥厚 乌头赤石脂丸 氧化应激 细胞凋亡 Keap1/Nrf2/HO-1/NQO-1信号通路 

分 类 号：R285.5[医药卫生—中药学]