白藜芦醇减轻大鼠心肌缺血再灌注损伤作用的研究  

Resveratrol alleviates myocardial ischemia-reperfusion injury in rats

作　　者：邴森 张荣怀[2] 张学军[2] 朱舜明[2] BING Sen;ZHANG Ronghuai;ZHANG Xuejun;ZHU Shunming(Department of Cardiology,Xi’an No.3 Hospital,Xi’an 710068,China;First Department of Cardiology,Shaanxi Provincial People’s Hospital)

机构地区：[1]西安市第三医院心内科,西安710068 [2]陕西省人民医院心内一科

出　　处：《山西医科大学学报》2020年第9期918-926,共9页Journal of Shanxi Medical University

基　　金：陕西省自然科学基础研究计划项目(2018JM7114)。

摘　　要：目的探讨白藜芦醇减轻大鼠心肌缺血再灌注(I/R)损伤的作用。方法将Sprague Dawley(SD)大鼠随机分为假手术组、I/R组和白藜芦醇组,每组15只。I/R组和白藜芦醇组大鼠通过结扎冠状动脉左前降支(LAD)建立心肌I/R损伤模型。缺血前45 min,白藜芦醇组大鼠腹腔注射30 mg/kg白藜芦醇溶液1 ml,假手术组和I/R组注射等体积的生理盐水。通过2,3,5-氯化三苯基四氮唑(TTC)染色检测心肌梗死面积,Heidenhain染色评估心肌损伤。分别检测各组大鼠血清心肌肌钙蛋白I(TnI)水平和心脏组织中的活性氧(ROS)和丙二醛(MDA)水平。免疫组织化学染色检测心肌组织中8-羟基-2-脱氧鸟苷(8-OHdG)的表达。Western blot分析心肌组织中肿瘤坏死因子受体相关因子2(TRAF2)、葡萄糖调节蛋白78(GRP78)、Bclin-1和微管相关蛋白轻链3(LC3Ⅱ/Ⅰ)的表达。将大鼠心肌细胞与200μg/ml白藜芦醇孵育24 h,然后对细胞进行缺氧/复氧处理,并检测细胞活力、细胞凋亡和细胞内Ca^2+浓度。结果白藜芦醇组大鼠的心肌梗死面积显著低于I/R组[(21.2±2.3)%vs(35.4±3.2)%,P<0.05]。白藜芦醇组大鼠的血清TnI水平显著低于I/R组(P<0.05)。白藜芦醇组大鼠的8-OHdG阳性染色细胞数显著低于I/R组(P<0.05)。白藜芦醇组大鼠的GRP78和TRAF2的蛋白表达水平显著低于I/R组(P<0.05)。白藜芦醇组大鼠的Bclin-1和LC3Ⅱ/Ⅰ的蛋白表达水平显著低于I/R组(P<0.05)。白藜芦醇显著提高了缺氧/复氧诱导的心肌细胞活力,抑制了细胞凋亡,降低了细胞内Ca^2+浓度(P<0.05)。结论白藜芦醇预处理可通过抑制氧化应激、内质网应激、自噬和Ca 2+内流来减轻心肌缺血再灌注损伤。Objective To explore the effect of resveratrol on myocardial ischemia-reperfusion(I/R)injury in rats.Methods Sprague Dawley(SD)rats were randomly divided into sham group,I/R group and resveratrol group(n=15 in each group).A myocardial I/R injury model was established by ligating the left anterior descending coronary artery(LAD)of rats in I/R group and resveratrol group.Rats were injected intraperitoneally with 1 ml of 30 mg/kg resveratrol solution 45 min before ischemia,and an equal volume of normal saline in sham group and I/R group.The area of myocardial infarction was detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining,and the myocardial damage was assessed by Heidenhain staining.The serum cardiac troponin I(TnI)level and the levels of reactive oxygen species(ROS)and malondialdehyde(MDA)in cardiac tissues of rats in each group were measured.Immunohistochemical staining was used to detect the expression of 8-hydroxy-2-deoxyguanosine(8-OHdG)in myocardial tissue.Western blot was used to evaluate the expression of TNF-αreceptor associated factor 2(TRAF2),glucose regulatory protein 78(GRP78),Bclin-1 and microtubule associated protein light chain 3(LC3Ⅱ/Ⅰ)in myocardium.Rat myocardial cells were incubated with 200μg/ml resveratrol for 24 h,and then cells were treated with hypoxia/reoxygenation,and cell viability,apoptosis and intracellular Ca 2+concentration were measured.Results The area of myocardial infarction in resveratrol group was significantly lower than that in I/R group[(21.2±2.3)%vs(35.4±3.2)%,P<0.05].Serum TnI level in resveratrol group was significantly lower than that in I/R group(P<0.05).The number of 8-OHdG positive staining cells in resveratrol group was significantly lower than that in I/R group(P<0.05).The protein expression levels of GRP78 and TRAF2 in resveratrol group were significantly lower than those in I/R group(P<0.05).The protein expression levels of Bclin-1 and LC3Ⅱ/Ⅰin resveratrol group were significantly lower than those in I/R group(P<0.05).Resveratrol significantl

关 键 词：白藜芦醇 心肌缺血再灌注损伤 氧化应激 内质网应激 自噬 Ca 2+ 

分 类 号：R965[医药卫生—药理学]