[1]宋华培,黄跃生,党永明,等.PI3K/Akt信号途径抑制烧伤后大鼠缺血缺氧心肌细胞凋亡[J].第三军医大学学报,2009,31(01):52-55.
 SONG Hua-pei,HUANG Yue-sheng,DANG Yong-ming,et al.PI3K/Akt signal pathway inhibits ischemia and hypoxia-induced myocardial apoptosis in rats[J].J Third Mil Med Univ,2009,31(01):52-55.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
31卷
期数:
2009年第01期
页码:
52-55
栏目:
论著
出版日期:
2009-01-15

文章信息/Info

Title:
PI3K/Akt signal pathway inhibits ischemia and hypoxia-induced myocardial apoptosis in rats
作者:
宋华培黄跃生党永明张东霞褚志刚张琼
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
Author(s):
SONG Hua-pei HUANG Yue-sheng DANG Yong-ming ZHANG Dong-xia CHU Zhi-gang ZHANG Qiong
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
关键词:
PI3K/Akt心肌细胞凋亡caspase-3p53Bax
Keywords:
PI3K/Akt cardiomyocytes apoptosis caspase-3 p53 Bax
分类号:
R322.11; R329.28; R644.02
文献标志码:
A
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3 h达高峰;烧伤3 h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。
Abstract:
Objective    To investigate the role and mechanisms of the PI3K/Akt signal pathway in the apoptosis of rat cardiomyocytes after ischemia and hypoxia due to severe burn injury.     Methods    Burn models of full-thick 30%TBSA burn injury were established by scalding rat back in hot water. The activation of the PI3K/Akt signal pathway was observed by Western blotting, and myocardial apoptosis was assessed by TUNEL. Cultured rat cardiomyocytes under ischemic/hypoxic conditions were divided into the control group, the ischemia and hypoxia group, and the LY294002 or IGF-1 treatment group. The apoptosis of cardiomyocytes were assessed by ELISA. The caspase-3 activity was measured by DEVD fluorescence. The transcriptional activity of p53, Bax was assessed by RT-PCR.     Results    After severe burn, PI3K and pAkt expressions increased gradually in the rat myocardial tissue, and reached a peak at 3 h postburn. At 3 h postburn, the apoptosis increased significantly in rats. When the PI3K/Akt pathway was specifically inhibited by LY294002, the myocardial apoptosis increased significantly in the burn group as compared with the control group (P<0.05). Cultured cardiomyocytes after ischemia and hypoxia showed the following changes:  increased apoptosis, gradually enhanced caspase-3 activity, gradually increased p53 and Bax mRNA expressions. Compared with the ischemia and hypoxia group, blockade of the PI3K/Akt pathway with LY294002 increased the number of apoptotic cardiomyo-cytes, caspase-3 activity, and p53 and Bax mRNA expression significantly (P<0.05). After activation of the PI3K/Akt pathway with IGF-1, caspase-3 activity decreased significantly (P<0.05), as compared with the ischemia and hypoxia group.     Conclusion    The PI3K/Akt signal pathway plays anti-apoptotic role in ischemic/hypoxic cardiomyocytes. PI3K/Akt pathway regulating p53 and Bax expression is probably the mechanism of anti-apoptosis, which can suppress the activity of caspase-3 and decrease the number of apoptotic cardiomyocytes.

参考文献/References:

宋华培, 黄跃生, 党永明, 等. PI3K/Akt信号途径抑制烧伤后大鼠缺血缺氧心肌细胞凋亡[J]. 第三军医大学学报, 2009, 31(1):52-55.

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更新日期/Last Update: 2009-01-06