急性心肌梗死时晚期糖基化终末产物受体表达水平的改变

目的 研究大鼠急性心肌梗死时心脏晚期糖基化终产物受体(RAGE)表达水平的改变.方法 将体重(230±20)g的SD大鼠随机分为实验组和假手术组,两组均在麻醉下打开胸腔挤出心脏,实验组用6号手术线在左心耳下1.5~2 mm处结扎冠状动脉左前降支建立急性心肌梗死模型,假手术组不结扎,之后将心脏放回胸腔,关闭切口;3周后处死大鼠,取心脏不同部位心肌组织,应用定量PCR技术检测RAGE基因mRNA表达水平;应用免疫组织化学和Western blot方法检测RAGE蛋白表达水平;应用Western blot方法检测ERK1/2蛋白表达水平.结果 实验组梗死区心肌组织RAGE的mRNA水平较非梗死区明显升高(P<0.05);免疫组织化学及Western blot分析显示梗死区RAGE蛋白表达水平明显较非梗死区高(P<0.05);梗死区pERK1/2蛋白表达水平明显高于非梗死区(P<0.05).假手术组心肌组织RAGE的mRNA和蛋白表达水平、pERK1/2蛋白表达水平与实验组非梗死区心肌组织比较差异无统计学意义(P>0.05).结论 大鼠心肌梗死后,梗死区心肌组织RAGE被激活,并通过MAPK/ERK1/2途径进一步激活核因子-κB等下游信号转导因子,最终引起一系列促炎反应并导致心肌重构.

The change of cardiac RAGE expression in acute myocardial infarction

Objective To investigate the change of cardiac RAGE expression level in myocardial infarction rat model.Methods Myocardial infarction rat model was constructed by LAD ligation in Spraguee Dawley rats (230±10)g.The mRNA level of RAGE in infarcted and non-infarcted regions of hearts was assessed by qPCR.The protein expression level was measured by immunohistochemistric and Western Blot analysis, and pERK1/2 levels were also detected by Western Blot analysis.Results The RAGE mRNA level of infracted regions was significantly higher than that in non-infarcted regions (P<0.05).The protein expression of RAGE in infarcted regions was significantly increased comparing with that in non-infarcted regions (P<0.05).The pERK1/2 expression level in infarcted regions was also significantly higher than that in non-infarcted regions (P<0.05).There was no significant difference in RAGE mRNA level, RAGE protein expression level or pERK1/2 expression level between cardiac tissue of Sham-operated group and non-infarcted regions of experimental group (P>0.05).Conclusion RAGE protein is activated in infarcted hearts tissues in rats, which increases the activation of MAPK/ERK1/2, subsequently leads to the activation of downstream cytokines, including NF-κB, finally induces overwhelming inflammatory and myocardial remodeling.