阿托伐他汀预处理对大鼠心肌缺血再灌注后不同时间点心肌组织中HIF-α和VEGF表达的影响  

Effects of atorvastatin pretreatment on expressions of HIF-αand VEGF at different time points in myocardium tissue of rats after myocardial ischemia reperfusion

作　　者：石博[1] 黄可欣[1] 叶保国[2] 张艳 黄可敬[4] 

机构地区：[1]吉林大学白求恩医学院形态学中心,吉林长春130021 [2]吉林大学第一医院麻醉科,吉林长春130021 [3]内蒙古自治区民族大学附属医院儿科,内蒙古通辽028007 [4]吉林省长春市中心血站检验科,吉林长春130033

出　　处：《吉林大学学报（医学版）》2013年第6期1159-1163,1312,1313,共7页Journal of Jilin University：Medicine Edition

基　　金：吉林省教育厅科研基金资助课题(2010268)

摘　　要：目的:探讨阿托伐他汀预处理(AT)对大鼠心肌缺血再灌注(I/R)后不同时间点心肌组织中缺氧诱导因子α(HIF-α)和血管内皮生长因子(VEGF)蛋白及mRNA表达的影响,阐明AT对大鼠心肌组织的保护作用。方法:健康雄性Wistar大鼠50只,随机分为假手术组、缺血30min再灌注2h模型组(I30min R2h组)、缺血30min再灌注6h模型组(I30min R6h组)、缺血30 min再灌注2h阿托伐他汀组(I30min R2h AT组,10mg·kg-1)和缺血30min再灌注6h阿托伐他汀组(I30min R6h AT组,10mg·kg-1),每组10只。I/R模型制备采用结扎左冠状动脉前降支(LAD)的方法。检测各组大鼠心肌梗死面积比,采用免疫组织化学法检测大鼠心肌组织中HIF-α和VEGF蛋白表达,采用RT-PCR法检测大鼠心肌组织中HIF-1和VEGF mRNA水平。结果:与假手术组比较,I30min R2h组、I30min R6h组大鼠心肌梗死面积比增大(P<0.01);与I30min R2h组和I30min R6h组比较,I30min R2h AT组和I30min R6h AT值大鼠心肌梗死面积比减少(P<0.01)。与假手术组比较,I30min R2h组、I30min R6h组、I30min R2h AT组和I30min R6h AT组大鼠HIF-α和VEGF蛋白表达水平及HIF-1和VEGF mRNA水平均显著升高(P<0.01);且I30min R6h组大鼠HIF-α和VEGF蛋白表达水平及HIF-1和VEGF mRNA水平低于I30min R2h组,I30min R6h AT组HIF-α和VEGF蛋白表达水平及HIF-1和VEGF mRNA水平低于I30min R2h AT组(P<0.01);与I30min R2h组比较,I30min R2h AT组大鼠HIF-α和VEGF蛋白表达水平和HIF-1及VEGF mRNA的水平均显著升高(P<0.01);与I30min R6h组比较,I30min R6h AT组大鼠HIF-α和VEGF蛋白表达水平和HIF-1及VEGF mRNA水平均显著升高(P<0.01)。结论:I/R损伤早期能引起HIF-α、VEGF蛋白和HIF-1、VEGF mRNA水平上调,AT可明显上调HIF-α、VEGF蛋白和HIF-1、VEGF mRNA水平,提示AT对大鼠心肌组织具有保护作用。Objective To explore the effects of atorvastatin pretreatment （AT） on the expressions of HIF-α and VEGF protein and mRNA at different time points in myocardium tissue of the rats after myoeardium ischemia reperfusion （I/R） and to elucidate the protective effect of AT on myocardium tissue of the rats. Methods 50 healthy male Wistar rats were randomly divided into sham operation group, ischemia 30 min reperfusion 2 h model （I30minR2h） group, ischemia 30 min reperfusion 6 h model （I30minR6h） group, ischemia 30 min reperfusion 2 h atorvastatin （I30min R2hAT, 10 mg · kg-1 ） group, and ischemia 30 min reperfusion 6 h atorvastatin （I30min R6hAT, 10 mg · kg 1） group; there were 10 rats in each group. I/R model was prepared by ligating the left anterior descending coronary artery （LAD） method. The ratios of mypcordial infarction area of the rats in various groups were detected, the expressions of HIF-α and VEGF protein were detected with immunohistochemical method in myocardium tissue of the rats, the expression levels of HIF-α and VEGF mRNA in myocardium tissue of the rats were detected by RT PCR method. Results Compared with sham operation group, the ratios of myocardial infarction area of the rats in I30min R2h group and I30min R6h group were increased （P〈0.01） ; the ratios of myocardial infarction area of the rats in I30min R2h AT group and I30min R6h group were lower than those in I30min R2h group and Ia0minR6h group （P〈0.01）. Compared with sham operation group, the expression levels of HIF-α and VEGF protein and HIF-α and VEGF mRNA in I30minR2a group, I30min Rsh group, I30min R2h AT group, and I30min R6h AT group were significantly increased （P〈0.01）; the expression levels of HIF a and VEGF protein and HIF-α and VEGF mRNA of the rats in I30min R6h group were lower than those in I30min R2h group, and the expression levels of HIF-α and VEGF protein and HIF-a and VEGF mRNA of the rats in I30min R6h AT group were lower than those in I30min R2h AT group （P〈0.01�

关 键 词：心肌缺血再灌注 阿托伐他汀 阿托伐他汀预处理 缺氧诱导因子α 血管内皮生长因子 

分 类 号：R972.4[医药卫生—药品]