Caspase-8和Caspase-3在大鼠急性心肌损伤中的作用及药物预处理对其影响

THE ROLE OF CASPASE-8 AND CASPASE-3 ON THE MYOCARDIAL INJURY INDUCED BY ISOPRENALINE AND THE EFFECT OF bFGF ON CASPASE-8 AND CASPASE-3

目的:研究半胱天冬酶-8(caspase-8)、半胱天冬酶-3(caspase-3)在异丙基肾上腺素(isoprena-line,Iso)致大鼠急性心肌损伤心肌细胞凋亡中的作用及碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)预处理对其影响。方法:将Wistar大鼠随机分成三组:对照组、Iso损伤组和bFGF预处理组,光镜观察心肌组织病理变化,TUNEL法检测心肌细胞凋亡,免疫组化和RT-PCR法检测caspase-8、caspase-3蛋白及mRNA的表达水平,底物降解法测定酶活性。结果:损伤组心肌坏死较重,心肌细胞凋亡显著,且caspase-8、caspase-3蛋白及mRNA的表达水平明显升高,酶活性增加;预处理组心肌坏死明显减轻,细胞凋亡减少,caspase-8、caspase-3蛋白及mRNA的表达水平明显下降,酶活性受抑制。结论:bFGF预处理可能通过抑制caspase-8、caspase-3的表达及酶活性以减少心肌细胞凋亡从而减轻大鼠心肌损伤。

Objective： To study the role of caspase - 8, caspase - 3 on the myocardial injuy induced by isoprenaline and the effect of bFGF on caspase - 8, caspase - 3. Methods： Wistar rats were divided randomly into three groups： control group, iso group and bFGF group. The pathological changes were observed by microscope. The apoptosis were observed by TUNEL. The mRNA and protein ex-pression of caspase - 8, caspase - 3 were tested with immunohistochemistry and RT - PCR methods. The enzyme activity was tested by substrate degradation. Results：In the iso group, the myocardial necrosis were more serious, and there were more apoptosis, moreover, the expression of mRNA and protein of caspase - 8, caspase - 3 increased, and the enzyme activity of caspase - 8 ,caspase - 3 went up.In the bFGF group, the myocardial necrosis were relieved and there less apoptosis. The expression of mR-NA and protein of caspase-8 ,caspase -3 decreased clearly. Conclution：The bFGF can alleviate rat myoeardium from injury by inhibiting the expression and activity of caspase - 8 ,easpase - 3 and reducing myocardial apoptosis.