急性心肌梗死大鼠心肌细胞凋亡及凋亡相关蛋白表达的研究

目的　探讨急性心肌梗死 (AMI)大鼠心肌细胞凋亡及凋亡相关蛋白P5 3、Fas、Bax和Bcl 2的表达。方法　雄性SD大鼠 10 9只 ,其中 10 1只结扎冠状动脉左前降支 ,80只术后存活分入 10个时点 ,每时点 8只 ,另 8只大鼠开胸暴露左冠状动脉但不结扎作假手术组。于AMI后 1、3、6、12及 2 4h和 2、3、5、7及 14d分别以原位末端标记(TUNEL)法和免疫组织化学方法检测心肌细胞凋亡和心肌组织P5 3、Fas、Bax和Bcl 2蛋白的表达。结果　 8只假手术大鼠心肌组织仅有少量的凋亡细胞 ,P5 3、Fas和Bcl 2的免疫反应阳性 ,而Bax的免疫反应为阴性。AMI后 1h梗死区周围心肌的凋亡细胞阳性指数开始升高 ,3d达高峰 ,14d仍高于假手术组 ;P5 3、Fas、Bax和Bcl 2分别于 6h、12h、12h和 3h开始升高 ,于 2d、3d、2 4h和 2d达高峰 ,然后逐渐下降 ,14d与假手术组比较差异无显著性意义。结论　AMI大鼠心肌细胞凋亡增加 ,心肌组织的凋亡相关蛋白P5 3、Fas、Bax和Bcl 2的表达也增加

Cardiomyocyte apoptosis and expression of apoptotic genes in acute myocardial infarction of rats

Objective To determine the changes of cardiomyocyte apoptosis and expression of P53,Fas,Bax and Bcl 2 in a rat model of acute myocardial infarction(AMI).Methods One hundred and nine male Sprague Dawley rats were used in this study.Left anterior descending branch of coronary artery ligation produced extensive AMI in 80 of 101 animals surviving the initial surgery.The 80 survivaing animals were allocated to 10 time points,with 8 rats for each duration of infarction.The remaining eight animals undergoing thoracotomy but not coronary ligation served as sham operation controls.Apoptotic index,P53,Fas,Bax and Bcl 2 expression in myocardium were analyzed semiquantitatively by TUNEL or immunohistochemical means before (sham operation animals) and 1,3,6,12,24 hours and 2,3,5,7,14 days after coronary ligation.Results Only several apoptotic cardiomyocytes were seen in sham operation controls.Immunoreactive positions of P53,Fas and Bcl 2 were also manifested in these control sections.One hour after AMI,the apoptotic index significantly increased,reached a peak 3 days after ligation and then decreased gradually over the remaining 2 weeks.The increase in P53,Fas,Bax and Bcl 2 in the rats of AMI was evident at 6 hours,12 hours,12 hours and 3 hours,respectively;peaked on day 2, day 3,at 24 hours and on day 2 after ligation respectively and then declined gradually to the levels of sham operation controls.Conclusion The current investigation shows that cardio myocyte apoptosis is increased and the expression of P53,Fas,Bax and Bcl 2 in myocardium is also increased in this model,suggesting that they may take part in regulating the cardiomyocyte apoptosis in the rat model of AMI.