PI3K/Akt信号途径抑制烧伤后大鼠缺血缺氧心肌细胞凋亡

被引：33

作者：

宋华培

黄跃生

党永明

张东霞

褚志刚

张琼

机构：

[1] 第三军医大学西南医院全军烧伤研究所创伤、烧伤与复合伤国家重点实验室

来源：

第三军医大学学报 | 2009年 / 31卷 / 01期

基金：

国家自然科学基金重点项目;

关键词：

PI3K/Akt; 心肌细胞; 凋亡; caspase-3; p53; Bax;

D O I：

暂无

中图分类号：

R644 [烧伤及烫伤（灼伤）];

学科分类号：

100227 [皮肤病学];

摘要：

目的探讨PI3K/Akt信号途径在烧伤后大鼠缺血缺氧心肌细胞凋亡中的作用及机制。方法首先建立模拟烧伤的动物模型,通过Western blot观察PI3K/Akt信号途径的活化规律,TUNEL实验观察烧伤大鼠心肌凋亡。然后建立离体培养的缺血缺氧心肌细胞模型,并分为对照组、单纯缺血缺氧组、LY294002处理组或IGF-1处理组,应用ELISA观察缺血缺氧心肌细胞凋亡。并通过DEVD荧光检测caspase-3酶活性,RT-PCR检测p53、Bax的转录活性。结果烧伤后大鼠心肌组织内PI3K和pAkt表达逐渐增加,伤后3h达高峰;烧伤3h后,大鼠心肌细胞凋亡率显著增加;应用LY294002特异性抑制PI3K/Akt通路后,大鼠心肌细胞凋亡率较对照组增加更为显著(P<0.05)。缺血缺氧导致体外培养心肌细胞凋亡增加,caspase-3活性逐渐增强,p53、Bax mRNA表达量逐渐升高;与单纯缺血缺氧组相比,应用LY294002阻断PI3K/Akt途径活化后,心肌细胞凋亡数量增加更显著(P<0.05),caspase-3活性增高更为明显(P<0.05),p53、Bax mRNA表达量均显著升高(P<0.05);用IGF-1预先激活PI3K/Akt途径后,与单纯缺血缺氧组比较,心肌细胞caspase-3活性明显降低(P<0.05)。结论PI3K/Akt信号途径在缺血缺氧心肌细胞中具有抗凋亡作用,该作用与PI3K/Akt调控促凋亡基因p53、Bax的表达,抑制caspase-3凋亡反应有关,并为心肌缺血缺氧损害的临床防治提供新思路及实验依据。

引用

页码：52 / 55

页数：4

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