黄芪甲甙对急性心肌梗死大鼠心室重构和NOX/ROS/TNFα信号通路的影响  

Effects of AstragalosideⅣon Ventricular Remodeling and NOX/ROS/TNF-αSignaling Pathways in Rats with Acute Myocardial Infarction

作　　者：赵佩 邹青 李泽霖 ZHAO Pei;ZOU Qing;LI Zelin(Department of Cardiovascular Medicine,the Second Affiliated Hospital of Air Force Medical University,Xi’an 710038,China)

机构地区：[1]空军军医大学第二附属医院心血管内科,西安710038

出　　处：《生物技术进展》2022年第5期778-785,共8页Current Biotechnology

基　　金：空军军医大学第二附属医院科技创新发展基金项目(院医〔2020〕73号)。

摘　　要：研究旨在探究黄芪甲甙对急性心肌梗死大鼠心室重构的作用及其机制。选取36只Wistar大鼠随机分为假手术组、模型组、黄芪甲甙低剂量组、黄芪甲甙中剂量组、黄芪甲甙高剂量组和阳性对照组,每组6只。除假手术组外,其余大鼠手术建立急性心肌梗死模型,假手术组大鼠开胸后仅分离冠状动脉左前降支,不做结扎处理便逐层缝合,造模后第2天开始药物干预:黄芪甲甙低、中、高剂量组分别给予20、40、60 mg·kg^(-1)黄芪甲甙灌胃处理,阳性对照组给予100 mg·kg^(-1)阿司匹林灌胃处理。比较各组治疗第0、2、4周心功能指标[左心室射血分数(left ventricular ejection fractions,LVEF)、左心室短轴缩短率(left ventricular fractional shortening,LVFS)、左心室质量指数(left ventricular mass index,LVMI)]的变化情况。采用心脏血流动力学监测系统监测心脏血流动力学指标[左心室舒张末压(left ventricular end diastolic pressure,LVEDP)、左心室收缩压(left ventricular systolic pressure,LVSP)和左心室等容收缩/舒张压上升最大速率(maximal rate of left ventricular pressure increase/decrease,±dp/dtmax)]的变化情况,采用酶联免疫吸附法测定血清血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)、内皮素1(endothelin-1,ET-1)、脑钠肽(brain natriuretic peptide,BNP)含量,试剂盒检测心肌组织活性氧(reactive oxygen species,ROS)含量,实时荧光定量PCR和Western blot检测大鼠心肌组织NADPH氧化酶(reduced nicotinamide adenine dinucleotide phosphate oxidase,NOX)、肿瘤坏死因子α(tumor necrosis factorα,TNF-α)mRNA相对表达量和蛋白表达水平。结果显示,治疗4周后,黄芪甲苷高剂量组和阳性对照组LVEF、LVFS随着治疗时间延长不断升高(P<0.05);与相同治疗时间假手术组比较,模型组LVEF、LVFS均显著降低(P<0.05);与治疗第0周模型组比较,各治疗组LVEF、LVFS差异无统计学意义(P>0.05);治疗第2、4周与模型组比较,黄芪甲苷中�The aim of this study was to explore the role and mechanism of AstragalosideⅣon ventricular remodeling in rats with acute myocardial infarction.36 Wistar rats were selected and randomly divided into sham operation group,model group,low-dose AstragalosideⅣgroup,middle-dose AstragalosideⅣgroup,high-dose AstragalosideⅣgroup and positive control group,with 6 rats in each group.Except for the sham operation group,the remaining rats were operated to establish rat models of acute myocardial infarction.Rats in the sham operation group were only separated from the left anterior descending coronary artery after thoracotomy and then sutured layer by layer without ligation,and received drug intervention on the 2nd day after modeling.The low-dose,middle-dose and high-dose AstragalosideⅣgroups were given AstragalosideⅣby gavage at the dos⁃es of 20,40 and 60 mg·kg^(-1) respectively,and the positive control group was given 100 mg·kg^(-1) of aspirin by gavage.The car⁃diac function indicators[left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventric⁃ular mass index(LVMI)]were compared among the groups on the 0th,2nd and 4th week of treatment.Cardiac hemodynamic monitoring system was applied to detect the cardiac hemodynamic indicators[left ventricular end diastolic pressure(LVEDP),left ventricular systolic pressure(LVSP),maximum rise rate of left ventricular pressure increase/decrease(±dp/dtmax)].The levels of serum angiotensinⅡ(AngⅡ),endothelin 1(ET-1)and brain natriuretic peptide(BNP)were mea⁃sured by enzyme-linked immunosorbent assay.Kit was used for detection of myocardial tissue reactive oxygen species(ROS)content,and real-time fluorescence quantitative PCR and Western blot were adopted to detect the mRNA relative expression levels and protein expression levels of NADPH oxidase(reduced nicotinamide adenine dinucleotide phosphate oxidase,NOX)and tumor necrosis factorα(TNF-α)in myocardial tissues of rats.Results showed that,after 4 weeks of treatment,the LVEF

关 键 词：黄芪甲甙 急性心肌梗死 心室重构 NOX/ROS/TNF-α信号通路 

分 类 号：R285.5[医药卫生—中药学]