目的观察脂联素(adiponectin,APN)对大鼠缺血/再灌注(ischemia/reperfusion,I/R)诱导的心肌细胞凋亡与凋亡相关蛋白Bcl-2、Bax、Caspase-3表达的影响。方法将48只大鼠随机分成假手术组(sham group)、I/R组(I/R group)、脂联素预处理组(APN+I/R group),每组16只。结扎左冠状动脉前降支,建立大鼠心肌I/R模型。各组随机选取8只,采用Evans blue-TTC双染法测定心肌梗死面积;另外8只对心功能指标进行监测,实验结束后,采用透射电镜观察心肌组织损伤;原位末端标记(TUNEL)法观察心肌细胞凋亡情况;Western blot法测定心肌Bcl-2、Bax、Caspase-3蛋白的表达。结果脂联素明显减小I/R所致的大鼠心肌梗死面积(P〈0.05),改善心脏血流动力学(P〈0.05),减轻透射电镜下心肌细胞形态、细胞膜、细胞核、线粒体等结构改变,减少细胞凋亡,增加Bcl-2表达(P〈0.05),降低Bax与Caspase-3蛋白表达(P〈0.05)。结论脂联素对I/R损伤的保护作用与抑制心肌细胞凋亡,从而减少心肌细胞损失、减轻心脏功能障碍有关,其抗凋亡作用机制可能与上调Bcl-2表达,下调Bax及Caspase-3表达有关。
Aim To study the effect of adiponectin(APN) on cardiomyocyte apoptosis and the expression of Bcl-2,Bax,Caspase-3 in rats with ischemia/reperfusion(I/R).Methods The I/R injury model was established by occluding the left anterior descending branch of coronary artery for 30 min and removing the ligation later to reperfusion for 3 hours.Forty-eight rats were divided into 3 groups randomly: sham group,I/R group and APN+I/R group.The infarct size was determined by using Evens blue and TTC double dye staining in 8 rats in each group.Others were monitored hemodynamics,then the ultrastructural change of myocardial tissue was observed by transmission electron microscope;cardiomyocyte apoptosis was marked by TUNEL;Bcl-2,Bax,Caspase-3 protein expression were tested by Western blot.Results APN pretreatment could decrease infarct size and ameliorate hemodynamics of I/R.APN also could inhibit cardiomyocyte apoptosis,increase the Bcl-2 protein expression(P〈0.05) and reduce the Bax and Caspase-3 protein expression(P〈0.05) in rats with myocardial ischemia/reperfusion.Conclusion The preexposure to APN provides protective effect on I/R injury,which is likely associated with the inhibition of cardiomyocyte apoptosis by up-regulating Bcl-2 protein expression and down-regulating Bax,Caspase-3 protein expression.