吉林大学学报(医学版)

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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

石博1,黄可欣1,叶保国2,张艳3,黄可敬4   

  1. 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
  • 收稿日期:2013-02-18 发布日期:2013-12-12
  • 通讯作者: 张 艳(Tel:0475-82121358,E-mail:1286425258@qq.com) E-mail:1286425258@qq.com
  • 作者简介:石 博(1968-),男,吉林省九台市人,实验师,主要从事病理免疫学的研究。
  • 基金资助:

    吉林省教育厅科研基金资助课题(2010268)

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

SHI Bo1,HUANG Ke-xin1,YE Bao-guo2,ZHANG Yan3,HUANG Ke-jing4   

  1. 1.Morphology Center,Normal Bethune College of Medicine,Jilin University,Changchun 130021,China;2. Department of Anesthesiology,First Hospital,Jilin University,Changchun 130021,China;3. Department of Pediatrics,Affiliated Hospital,Inner Mongolia University for Nationalities,Tongliao 028007,China;4. Department of  Laboratory,Changchun City Blood Center,Jilin Province,Changchun 130033,China
  • Received:2013-02-18 Published:2013-12-12

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30 min再灌注2 h模型组 (I30minR2h组)、缺血30 min再灌注6 h模型组(I30minR6h组)、缺血30 min再灌注2 h阿托伐他汀组(I30minR2hAT组,10 mg/kg)和缺血30 min再灌注6 h阿托伐他汀组(I30minR6hAT组,10 mg/kg),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,I30minR2h组、I30minR6h组大鼠心肌梗死面积比增大(P<0.01);与I30minR2h组和I30minR6h组比较,I30minR2hAT组和I30minR6hAT 值大鼠心肌梗死面积比减少(P<0.01)。与假手术组比较,I30minR2h组、I30minR6h组 、I30minR2hAT组和I30minR6hAT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I30minR6h组大鼠HIF-α和VEGF蛋白表达水平及HIF-1和VEGF mRNA水平低于I30minR2h组,I30minR6hAT组HIF-α和VEGF蛋白表达水平及HIF-1和VEGF mRNA水平低于I30minR2hAT组(P<0.01);与I30minR2h组比较,I30minR2hAT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I30minR6h组比较,I30minR6hAT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。

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&alpha, 血管内皮生长因子

Abstract:

Abstract: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 myocardium 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 (I30minR2hAT,10 mg/kg) group, and ischemia 30 min reperfusion 6 h atorvastatin (I30minR6hAT,10 mg/kg) 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 I30minR2h group and I30minR6h group were increased(P<0.01);the ratios of myocardial infarction area of the rats in I30minR2h AT group and I30min R6h group were lower than those in I30minR2h group and I30minR6h 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 I30minR2h group,I30minR6h group,I30min R2h AT group,and  I30min R6h AT group were significantly increased (P<0.01);the expression levels of  HIF-α and VEGF protein  and HIF-α and VEGF mRNA  of the  rats in I30minR6h group  were lower than  those in  I30minR2h group,and the expression levels of HIF-α and VEGF protein  and HIF-α and VEGF mRNA of the rats in I30minR6h AT group  were lower than  those in  I30minR2h AT group(P<0.01).Compared with I30minR2h group,the expression levels  of HIF-α and VEGF protein  and HIF-α and VEGF mRNA of the rats  in I30minR2h AT group were significantly increased(P<0.01);compared with I30minR6h group,the expression levels of HIF-α and VEGF protein  and HIF-α and VEGF mRNA of the rats in I30minR6h AT group were significantly  increased (P<0.01). Conclusion I/R injury  can  early cause up-regulation of the levels of HIF-α and VEGF protein and HIF-α and VEGF mRNA in rats,and AT  can significantly up-regulate the expression levels of HIF-α and VEGF protein and HIF-α and VEGF mRNA,which suggests that AT  has the protective effect on the myocardium tissue of rats.

Key words: myocardial ischemia reperfusion, atorvastatin, atorvastatin pretreatment, hypoxia inducible factor, vascular endothelial growth factor

中图分类号: 

  • R972.4