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宋华培,黄跃生,党永明,张东霞,褚志刚,张琼.PI3K/Akt信号途径抑制烧伤后大鼠缺血缺氧心肌细胞凋亡[J].陆军军医大学学报(原第三军医大学学报),2009,31(01):52-55.
SONG Hua-pei,HUANG Yue-sheng,DANG Yong-ming,ZHANG Dong-xia,CHU Zhi-gang,ZHANG Qiong.PI3K/Akt signal pathway inhibits ischemia and hypoxia-induced myocardial apoptosis in rats[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(01):52-55.
宋华培,黄跃生,党永明,张东霞,褚志刚,张琼.PI3K/Akt信号途径抑制烧伤后大鼠缺血缺氧心肌细胞凋亡[J].陆军军医大学学报(原第三军医大学学报),2009,31(01):52-55. DOI:
SONG Hua-pei,HUANG Yue-sheng,DANG Yong-ming,ZHANG Dong-xia,CHU Zhi-gang,ZHANG Qiong.PI3K/Akt signal pathway inhibits ischemia and hypoxia-induced myocardial apoptosis in rats[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(01):52-55. DOI:
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(P0.05)。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(P0.05),caspase-3活性增高更为明显(P0.05),p53、Bax mRNA表达量均显著升高(P0.05);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(P0.05)。 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。
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 (P0.05). 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 (P0.05). After activation of the PI3K/Akt pathway with IGF-1
caspase-3 activity decreased significantly (P0.05)
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.
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