牛磺酸对大鼠心肌缺血再灌注损伤心肌细胞凋亡的影响

Effects of Taurine on the Apoptosis of myocytes in Rats with Experimental Myocardial Ischemia/reperfusion Injury

目的 探讨牛磺酸对缺血再灌注损伤时心肌细胞凋亡的保护及初步机制。方法 采用在体结扎大鼠冠状动脉左前降支建立心肌缺血再灌注模型。以TUNEL法检测心肌凋亡细胞 ,免疫组化法分析心肌细胞Fas/FasL、Caspase 8及Caspase 3蛋白表达变化。荧光分析法测定Caspase 3活性。结果 凋亡组 (心肌缺血 1h ,再灌注 2 4h)心肌细胞凋亡指数为 (16 .3± 4 .5 2 ) ,较对照组 (0 .4 3± 0 .0 4 )有显著性升高 ,Fas/FasL及Caspase 3蛋白水平也均显著高于正常对照组 (P <0 .0 5 )。牛磺酸保护组的心肌细胞凋亡指数、Fas/FasL、Caspase 3蛋白水平及Caspase 3活性均显著性低于凋亡组。结论 牛磺酸对缺血再灌注损伤心肌细胞凋亡有较好的拮抗作用 ,其机制可能与降低Fas死亡受体通路中相关蛋白酶水平及其活性有关。

Objective To investigate the protective effects o f taurine on the apoptosis of myocytes in rats with myocardial ischemia-reperfusi on injury.Methods Rat modes with myocardial ischemia-reperfusion i njury were established by occluding left coronary artery(LCA)and followed by rel ease of it with ligation.Fifty rats were divided randomly into control group(sha m operated for 24 h),apoptosis group(1h of ischemia followed by 24 h of reperfus ion),and taurine group(intraperitoneal injection of taurine 100 mg/kg,200 mg/kg or 300 mg/kg respectively before ischemia followed by 24 h of reperfusion).Termi nal deoxynucleotidy transferase-mectiatde dUTP fluoescein nick end labeling(TUN EL)and S-P immunohistochemical staining were used respectively to determine the apoptosis and protein expression of Fas/Fasl and caspase-8/3 genes,and caspase -3 activity was detected by Fluorospectrophotometry.Results Apopto sis index,positive index of Fas/FasL and caspase-8/3 protein expression were al l increased in the rat's myocardium of apoptosis group,and the level of Caspase -3 activity increased.Taurine can significantly decrease apoptosis index, posit ive index of Fas/Fasl and caspase-8/3 protein expression, and caspase-3 activi ty in the ischemia-reperfusion myocardium.Conclusion Taurine exert s a good antagonist on the apoptosis of ischemia-reperfusion myocardial cells a nd signal transduction pathway of Fas death receptor.