缺血预适应对大鼠急性心肌梗死缺氧诱导因子1α表达的影响及蛋白激酶C信号通路的作用
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辽宁省自然科学基金(20062106)


The Impact of Ischemia-Preconditioning on Expression of Hypoxia Inducible Factor-1α Gene in Acute Myocardial Infarction Rats and the Involvement of PKC Signal Pathway
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    目的研究缺血预适应后急性心肌梗死缺氧诱导因子1α表达的变化及蛋白激酶C的信号传导作用。方法选择雄性Wistar大鼠32只,随机分为4组:缺血预适应组、单纯急性心肌梗死组、缺血预适应加蛋白激酶C抑制剂组和假手术组。缺血预适应加蛋白激酶C抑制剂组预适应前10min静脉注射蛋白激酶C抑制剂白屈菜季铵碱5mg/kg,然后结扎左前降支;假手术组不结扎左前降支。1天后,10%水合氯醛腹腔注射麻醉,活体取出心脏,测量心肌梗死面积,测定缺氧诱导因子1α和血管内皮生长因子mRNA表达,蛋白印记分析检测缺氧诱导因子1α和血管内皮生长因子蛋白的表达,术前术后测定血管内皮生长因子含量。结果缺氧诱导因子1αmRNA表达,缺血预适应组明显增加(P<0.01),缺血预适应加蛋白激酶C抑制剂组与单纯急性心肌梗死组差异无显著性(P>0.05),其蛋白表达有相同的变化。缺血预适应加蛋白激酶C抑制剂后,缺氧诱导因子1αmRNA表达明显减少(P<0.01),其靶基因血管内皮生长因子mRNA表达也明显减少,其蛋白表达有相同的变化。缺血预适应组心肌梗死面积(24.18%±2.25%)明显小于缺血预适应加蛋白激酶C抑制剂组(38.11%±2.94%)和单纯急性心肌梗死组(37.73%±3.32%;P<0.01)。结论缺氧诱导因子1α的表达是缺血预适应重要的内源性保护机制,其表达是依赖于蛋白激酶C的激活,蛋白激酶C是缺氧诱导因子1α表达的重要信号传导通路。

    Abstract:

    Aim To study the expression of hypoxia-inducible factor-1α(HIF-1α) in myocardial infarction rats and the role of protein kinase C (PKC) in signal pathway of hypoxia-inducible factor-1α gene expression. Methods 32 healthy male Wistar rats were divided into four groups:ischemic preconditioning group,simple myocardial infarction group,ischemic preconditioning plus protein kinase C inhibitor group and sham-operation group. Rats in treated groups received ligation of the proximal left anterior descending coronary artery to induce acute myocardial infarction. The sham-operation group dont take ligation of coronary artery. In ischemic preconditioning plus PKC inhibiter group,rats were injected with the protein kinase C inhibitor (chelerythrine,5 mg/kg,iv). After 1 day of operation,rats were killed. Results The infarct size in ischemic preconditioning group decreased significantly than that in ischemic preconditioning plus protein kinase C inhibitor group and simple myocardial infarction group (P<0.01). The hypoxia-inducible factor-1α mRNA gene expression increased in ischemic preconditioning group more than that in ischemic preconditioning plus protein kinase C inhibitor group and simple myocardial infarction group. Hypoxia-inducible factor-1α protein expression had the same change. Conclusions Hypoxia-inducible factor-1α play aprotective role in ischemic preconditioning; protein kinase C is the important signal pathway of hypoxia-inducible factor-1α gene expression.

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牛铁生,齐国先,付鹏,孙英贤.缺血预适应对大鼠急性心肌梗死缺氧诱导因子1α表达的影响及蛋白激酶C信号通路的作用[J].中国动脉硬化杂志,2008,16(10):796~800.

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  • 收稿日期:2008-09-03
  • 最后修改日期:2008-10-18
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