【摘要】 目的:研究腺病毒介导的低氧诱导因子-1α(HIF-1α)基因转染入兔急性心肌梗死(AMI)边缘区缺血心肌后,HIF-1α、细胞外信号调节激酶(ERK)、磷酸化细胞外信号调节激酶(p-ERK)的蛋白表达情况,初步探讨HIF-1α的作用机制。方法:建立兔AMI模型,随机分为4组,分别于心肌内注入腺病毒介导的HIF-1α基因(Ad-HIF-1α)、不含HIF-1α基因腺病毒颗粒(Ad-Blank)、HIF-1α核酶基因(Rz-HIF-1α),假手术组为对照,免疫组化和免疫印迹(Western blot)方法检测HIF-1α、ERK及p-ERK的蛋白表达。结果:AMI后1天外源性HIF-1α蛋白及p-ERK蛋白表达开始升高,7天达高峰,14、28天逐渐下降,56天时外源性HIF-1α蛋白及p-ERK蛋白均无表达,ERK在各时间点均有表达。在各组中,ERK含量基本无差异,p-ERK的蛋白含量在Ad-Blank组较Sham组升高,较Ad-HIF-1α组降低,Rz-HIF-1α组最低。结论:腺病毒介导的HIF-1α基因在缺血心肌能够有效表达,并能促进ERK的磷酸化,HIF-1α核酶基因能有效阻断缺血心肌HIF-1α的保护作用。更多还原

【Abstract】 Objective:To study the protein expression about the HIF-1α,ERK and p-ERK on ischemic myocardium after acute myocardiac infarction(AMI)and to explore initially the mechanism about HIF-1α.Methods:Rabbits AMI model were establised, and divided into 4 groups at random,and infected with Ad-HIF-1α,Ad-Blank,Rz-HIF-1αrespectively.Sham group was regarded as control.The protein expression of HIF-1α,ERK and p-ERK was detected by immunohistochemistry and Western-blot.Results:The protein expression of exogenous HIF-1αand p-ERK increased at 1d after AMI,reached the peak at 7d and decreased gradually at 14d and 28d.At 56d,the protein of HIF-1αand p-ERK was not expressed.Among four groups,there was no difference in the protein level of ERK,while p-ERK protein expression was higher in group Ad-Blank than that in group Sham,lower than that in group Ad-HIF-1α,and the protein level of p-ERK was the lowest in group Rz-HIF-1α.Conclusion:Ad-HIF-1αwas transducted effectively and promote ERK phosphorylated.HIF-1αribozyme gene can block the protective effect of HIF-1αon the ischemic myocardium.更多还原