犬急性心肌梗死晚期再灌注对心肌Fas/FasL系统的影响及其可能的氧化应激机制

Effect of Fas/FasL on late reperfusion of acute myocardial infarction and the potential oxidative stress mechanism in canine

目的:探讨急性心肌梗死晚期再灌注对心肌细胞凋亡基因Fas/FasL表达的影响及其可能的氧化应激机制。方法:18条健康成年杂种犬,按随机方法分为3组,每组6条。晚期再灌注组:结扎冠状动脉前降支6 h后再灌注6 h;持续缺血组:开胸后6 h,结扎冠状动脉前降支6 h,不行再灌注处理;对照组:冠状动脉前降支只穿线不结扎持续12 h。免疫组化法检测梗死边缘区心肌Fas和FasL蛋白表达,TUNEL法测心肌细胞凋亡指数(AI),比色法测定心肌超氧化物歧化酶(SOD)活性、还原性谷胱甘肽酶(GR)活性、丙二醛(MDA)含量等。结果:心肌Fas和FasL蛋白表达以及细胞凋亡指数在持续缺血组和晚期再灌注组明显高于对照组(分别为P<0.05,P<0.01),而且晚期再灌注组明显高于持续缺血组(P<0.05)。持续缺血组和晚期再灌注组的心肌细胞SOD活性和GR活性明显低于对照组(分别为P<0.05,P<0.01),而MDA含量均明显高于对照组(P<0.05),并且两组之间亦有显著差别(P<0.05)。结论:AM I晚期再灌注使梗死边缘区心肌细胞Fas/FasL蛋白表达以及细胞凋亡指数增加,提示晚期再灌注仍然存在再灌注损伤,其机制可能与氧化应激有关。

AIM： To discuss the effect of Fas/FasL on the late reperfusion of acute myocardial infarction （AMI） and the potential oxidative stress mechanism. METHODS： Eighteen anesthetized dogs were randomly divided into three groups： late reperfusion group （n =6） ： ligated the coronary for 6 h, followed by reperfusion for 6 h; permanent ischemia group （n =6） ： after pericardium were opened for 6 h, ligated the coronary for 6 h, and did not reperfuse; control group （n =6） ： did not ligate the coronary but operation last for 12 h. Infarction brim myocardial Fas/FasL was detected by immunohistochemistry. Apoptosis index （AI） was detected by TUNEL. SOD and GR activity and MDA content were detected by colorimetry. RESULTS： The expression of Fas/FasL and apoptosis index were significantly higher in permanent ischemia group and late reperfusion group than those in control group （ P 〈 0. 05, P 〈 0. 01 ）, and the difference between them was also significant （ P 〈 0. 05 ）. SOD and GR activities were lower in permanent ischemia group and late reperfusion group than those in control group （P 〈0. 05, P 〈0. 01）. The MDA contents in permanent ischemia group and late repeffusion group were higher than that in control group （ P 〈 0. 05 ）. CONCLUSION ： The late reperfusion of AMI promotes the expression of Fas/FasL and myocardial apoptosis, and it may be due to oxidative stress mechanism.