别嘌呤醇对缺血再灌注心肌P38MAPK活化和凋亡的影响

目的:探讨别嘌呤醇对心肌再灌注时P38MAPK活化和细胞凋亡的影响及其机制。方法:36只大耳白兔分为三组:缺血再灌注组,别嘌呤醇干预组和假手术组,检测再灌注15min时三组心肌中磷酸化P38MAPK(P-P38)的表达及再灌注4h后凋亡心肌数量。结果:假手术组P-P38表达极少,无核转位。缺血再灌注组心肌P-P38多,有核转位。别嘌呤醇干预组P-P38表达较缺血再灌注组减弱,核转位不明显。别嘌呤醇干预组再灌注4h后心肌凋亡指数较缺血再灌注组明显减少。结论:别嘌呤醇能抑制心肌再灌注时P38MAPK活化,减少细胞凋亡。

Changes of P38MAPK and apoptosis during myocardial ischemia/reperfusion in rabbits and effect of Allopurinol on them

Objective To investigate the signaling pathway involved in the Allopurinol-elicited anti-apoptotic effect during myocardial ischemia and reperfusion（I/R）in vivo.Method Domestic rabbits were anesthetized and subjected to 45 min of myoccardial ischemia followed by 15 min or 4 h reperfusion.Rabbits were randomly treated with Allopurinol 2 days before operation.Cardiac myocyte apoptosis was determined quantitatively by flow cytometry.Activations of P38 mitogen-activated protein kinase（MAPK）was determined by immunohistochemistry,and the density of the products was determined by image analysis.Results MI/R caused significant myocardium apoptotic death.Treatment with Allopurinol produced a significant anti-apoptotic effect as evidenced by a marked reduction of apoptotic index.In addition,P-P38 expressed in cytoplasm and nucleus in I/R group.Administration of Allopurinol reduced the expression of it.Conclusion In vivo treatment with Allopurinol before ischemia significantly reduces post-reperfusion apoptosis via the P38MAPK signaling pathway.