氯沙坦对大鼠急性心肌梗死的保护作用及其机制  

Protective effect of losartan on acute myocardial infarction in rats and its mechanism

作　　者：刘振[1] 韩明磊[1] 崔佳佳 侯永兰[1] 徐光翠 LIU Zhen;HAN Minglei;CUI Jiajia;HOU Yonglan;XU Guangcui(Department of Cardiovascular Medicine,Xinxiang Central Hospital,Xinxiang 453000,China;Department of Toxicology,School of Public Health,Xinxiang Medical College,Xinxiang 453000,China)

机构地区：[1]河南省新乡市中心医院心血管内科,河南新乡453000 [2]新乡医学院公共卫生学院毒理学教研室,河南新乡453000

出　　处：《吉林大学学报（医学版）》2021年第6期1397-1406,共10页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金青年基金项目(81703183);河南省卫健委医学科技攻关计划联合共建立项项目(LHGJ20200937)。

摘　　要：目的:探讨血管紧张素Ⅱ受体1(AT1R)阻断剂氯沙坦对急性心肌梗死(AMI)大鼠心肌损伤和心肌修复的影响,并阐明其作用机制。方法:45只大鼠采用冠脉结扎法建立AMI模型,将建模成功的39只大鼠随机分为模型组、AT1R阻断剂组和卡维地洛组,每组13只,另取13只大鼠作为假手术组。AT1R阻断剂组大鼠给予10 mg·kg^(-1)氯沙坦灌胃,卡维地洛组大鼠给予10 mg·kg^(-1)卡维地洛灌胃。采用小型动物超声诊断系统检测各组大鼠左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)和左心室射血分数(LVEF),ELISA法检测各组大鼠血清ELISA法检测各组大鼠血清肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)、乳酸脱氢酶(LDH)和脑钠肽前体(Pro-BNP)水平,2,3,5-三苯基氯化四氮唑(TTC)法检测各组大鼠心肌梗死面积百分率,HE染色观察各组大鼠心肌组织损伤情况,TUNEL染色检测各组大鼠心肌组织中TUNEL阳性细胞率,免疫组织化学染色检测各组大鼠心肌组织中硫氧还蛋白1(Trx1)和硫氧还蛋白还原酶1(TrxR1)表达情况,Western blotting法检测各组大鼠心肌组织中Trx1、TrxR1、烟酰腺嘌呤二核苷磷酸(NADPH)、裂解的Caspase 3(cleaved Caspase 3)、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:与假手术组比较,模型组大鼠LVESD和LVEDD升高(P<0.05),LVEF降低(P<0.05),血清CK-MB、cTnI、LDH及Pro-BNP水平均升高(P<0.05),心肌梗死面积百分率明显升高(P<0.05),心肌组织出现明显的病理改变,且TUNEL阳性细胞率升高(P<0.05),心肌组织中Trx1和Bcl-2蛋白表达水平降低(P<0.05),TrxR1、cleaved Caspase 3蛋白及Bax蛋白表达水平升高(P<0.05)。与模型组比较,AT1R阻断剂组和卡维地洛组大鼠LVESD和LVEDD降低(P<0.05),LVEF升高(P<0.05),血清CK-MB、cTnI、LDH和Pro-BN水平降低(P<0.05),心肌梗塞面积百分率降低(P<0.05),心肌组织病理改变得到明显改善,TUNEL阳性细胞率降低(P<0.05),心肌组织Objective:To investigate the effects of angiotensinⅡtype 1 receptor(AT1R)blocker losartan on the myocardial injury and myocardial repair of the acute myocardial infarction(AMI)rats,and to clarify their mechanisms.Methods:Forty-five rats were used to establish the AMI rat models by using the coronary artery ligation.A total of 39 rats were successfully modeled and were randomly divided into model group,AT1R blocker group,and carvedilol group,and there were 13 rats in each group.Another 13 rats were selected as sham operation group.The rats in AT1R blocker group were given 10 mg·kg^(-1) losartan by gavage,and the rats in carvedilol group were given 10 mg·kg^(-1) carvedilol by gavage.The left ventricular end systolic diamension(LVESD),left ventricular end diastolic diamension(LVEDD)and left ventricular ejection fraction(LVEF)of the rats in various groups were detected by the small animal ultrasonic diagnostic system.The serum levels of creatine kinase isozyme-MB(CK-MB),cardiac troponin I(cTnI),lactate dehydrogenase(LDH)and brain natriuretic peptide precursors(Pro-BNP)of the rats in various groups were detected by ELISA method.2,3,5-triphenyltetrazolium chloride(TTC)method was used to detect the percentages of myocardium infarction areas of the rats in various groups.HE staining was used to observe the morphology of myocardium tissue of the rats in various groups.TUNEL staining was used to detect the percentages of TUNEL positive cells of the rats in various groups.Immunohistochemical staining was used to detect the expressions of thioredoxin 1(Trx1)and thioredoxin reductase 1(TrxR1)in myocardium tissue of the rats in various groups.The protein expression levels of Trx1,TrxR1,nicotinyl adenine dinucleotide phosphate(NADPH),cleaved Caspase 3,B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax)in myocardium tissue of the rats in various groups were detected by Western blotting method.Results:Compared with sham operation group,the LVESD and LVEDD of the rats in model group were increased(P<0.05),while the LVE

关 键 词：急性心肌梗死 血管紧张素Ⅱ受体1 抗体硫氧还蛋白系统 心肌损伤 修复 

分 类 号：R542.22[医药卫生—心血管疾病]