厄贝沙坦对大鼠心肌缺血再灌注细胞凋亡与细胞外信号调节激酶通路的影响

目的观察厄贝沙坦对大鼠缺血再灌注心肌细胞凋亡的影响,并探讨其与细胞外信号调节激酶(ERK)通路的关系。方法健康雄性SD大鼠72只,随机分为假手术组、缺血再灌注组、缺血预处理组、厄贝沙坦组、厄贝沙坦+PD-98059组(PD组)。厄贝沙坦灌胃1周后制作大鼠心肌缺血再灌注模型,PD-98059于缺血前15 min尾静脉注射。实验结束后用TTC染色测定心肌梗死面积;免疫组织化学法检测心肌组织BcI-2、Bax表达;Western blot法测定磷酸化ERK的活性;TUNEL检测凋亡细胞指数。结果与假手术组比较,缺血再灌注组、缺血预处理组、厄贝沙坦组、PD组心肌细胞凋亡指数、磷酸化ERK活性及Bcl-2、Bax表达明显增加(P<0.01);与缺血再灌注组比较,缺血预处理组、厄贝沙坦组心肌梗死面积、心肌细胞凋亡指数和Bax表达明显降低,磷酸化ERK活性及Bcl-2表达明显增加(P<0.01);与厄贝沙坦组比较,缺血再灌注组、PD组心肌梗死面积、心肌细胞凋亡指数和Bax表达明显增加,磷酸化ERK活性及Bcl-2表达明显降低,差异有统计学意义(P<0.01)。结论厄贝沙坦能够激活ERK通路,进一步调控Bcl-2、Bax蛋白的表达,抑制再灌注心肌细胞的凋亡。

Effect of Irbesatan on ischemia reperfusion cardiomyocyte apoptosis and ERK pathway in rats

objective To research the effect of pretreatment with Irbesatan on ischemia reperfusion cardiomyocyte apoptosis and the relation between this effect and ERK pathway in rats,method 72 rats were randomly divided into sham operation,ischemia reperfusion,ischemic preconditioning, Irbesatan and Irbesatan+PD-98059(PD) group.PD-98059 was injected into tail vein at 15 min before ischemia.After lavage with Irbesatan for 7 days,rats were subjected to myocardial ischemia for 30 min,followed by reperfusion for 120 min.After reperfusion,infarct size was measured after staining by TTC;the expression of Bcl-2 and Bax was detected by immunohistochemistry;p-ERK vitality was measured by Western blot,and apoptosis index was detected by TUNEL.Results Compared with sham operation group,apoptosis index,p-ERK vitality,Bcl-2 and Bax expression were significantly increased in all the ischemia reperfusion,ischemic preconditioning,Irbesatan and PD group;compared with ischemia reperfusion group,infarct size,apoptosis index and Bax expression were significantly decreased in ischemic preconditioning and Irbesatan group,p-ERK vitality and Bcl-2 expression are increased;compared with Irbesatan group,infarct size,apoptosis index and Bax expression are significantly increased in ischemia reperfusion group and PD group, and p-ERK vitality and Bcl-2 expression are decreased(P<0.01).Conclusions Irbesatan can inhibit the ischemina reperfusion cardiomyocyte apoptosis,which mechanism may be related to the activation of ERK pathway and to the regulation of protein expression of Bcl-2 and Bax.