七氟醚后处理对大鼠心肌缺血再灌注时细胞凋亡的影响

Effects of sevoflurane postcondifioning on cardiomyocyte apoptosis during myocardial ischemia-reperfusion in rats

目的评价七氟醚后处理对大鼠心肌缺血再灌注时心肌细胞凋亡的影响。方法健康雄性Wistar大鼠45只，体重250—280g，采用随机数字表法，将大鼠随机分为3组（n=15）：假手术组（S组）、心肌缺血再灌注组（I／R组）和七氟醚后处理组（Spo组）。I／R组和Spo组采用结扎左冠状动脉前降支30min时进行再灌注120min的方法制备心肌缺血再灌注损伤模型，S组仅在左冠状动脉前降支下穿线。Spo组进行七氟醚后处理，于再灌注前1min时吸入七氟醚，呼气末浓度2．5％，持续5min。于再灌注120min时取左室心肌组织，测定缺血危险区和梗死区体积，计算缺血危险区和梗死区体积百分比。取左室缺血危险区心肌组织，测定心肌细胞凋亡指数，测定凋亡相关蛋白Bcl-2和Bax的蛋白及其mRNA的表达，计算Bcl-2／Bax比值。结果与s组比较，I／R组心肌梗死区体积百分比和心肌细胞凋亡指数升高，Bcl-2、Bax蛋白及mRNA表达上调，Bcl-2／Bax比值降低（P〈0．05）；与I／R组比较，Spo组心肌梗死区体积百分比和心肌细胞凋亡指数降低，Bax蛋白及mRNA表达下调，Bcl-2蛋白及mRNA表达上调，Bcl-2／Bax比值升高（P〈0．05）。结论七氟醚后处理通过上调Bcl-2表达，下调Bax表达，改善Bcl-2／Bax平衡，抑制心肌细胞凋亡，从而减轻大鼠心肌缺血再灌注损伤。

Objective To investigate the effects of sevoflurane postconditioning on cardiomyocyte apopto- sis during myocardial ischemia-reperfusion （I/R） in rats. Methods Forty-five healthy male Wistar rats weighing 250-280 g were randomly divided into 3 groups （ n = 15 each） ： group sham operation （ group S） ; group I/R and group sevoflurane pestconditioning （group Spo）. The animals were anesthetized with intraperitoneal 3% pentobarbital 45 mg/kg, tracheally intubated and mechanically ventilated. Myocardial I/R was produced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 rain reperfusion in groups I/R and Spo. In group Spo the animals inhaled 2.5 % sevoflurane for 5 min starting from 1 rain before reperfusion was started. The animals were sacrificed at the end of 120 min reperfusion. Their hearts were removed ,for measurement of in- farct size and the area at risk and determination of apoptotic index （the number of apoptotie cells/the total number of cells） and Bcl-2 and Bax protein and mRNA expression. Results Sevotlurane posteonditioning significantly re- duced infarct size in group Spo as compared with group HR. There was no significant difference in area at risk be- tween groups I/R and Spo. Myocardial I/R significantly increased the apoptotic index, Bcl-2 and Bax protein and mRNA expression in group I/R as compared with group S. Sevoflurane postconditioning significantly decreased apoptotic index and Bax protein and mRNA expression but increased Bcl-2 protein and mRNA expression in group Spo as compared with group I/R. Conclusion Sevoflttrane postconditioning attenuates myocardial I/R injury by reducing myocardial apoptosis, up-regulating Bcl-2 expression and dewn-regulating Bax expression.