糖原合成酶激酶-3与线粒体分裂蛋白在减轻大鼠心肌缺血再灌注损伤作用中的关系

The relationship between GSK-3 beta and Drp-1 in alleviating myocardial ischemia reperfusion injury in rats

目的探讨糖原合成酶激酶-3(GSK-3β)与线粒体分裂蛋白(Drp-1)在大鼠心肌保护中的关系。方法选取清洁健康雄性SD大鼠60只,体重250~300 g,随机分为4组(n=15):缺血再灌注组(IR组)、缺血再灌注+Mivi-1处理组(M组)、缺血再灌注+SB216763处理组(B组)、缺血再灌注+Mivi-1处理+SB216763处理组(D组)。采用结扎大鼠左冠状动脉前降支30 min,再灌注120 min的方法制备大鼠心肌缺血再灌注(MRIR)模型。M组再灌注前1 min静注Mivi-1(1.2 mg/kg);B组再灌注前1 min静注SB216763(0.2 mg/kg);D组再灌注前静注Mivi-1及SB216763。腹主动脉取血检测血清肌钙蛋白(cTnI)浓度;取心肌组织,TUNEL法检测细胞凋亡情况,计算凋亡指数(AI);观察心肌病理学结果;Western blot法检测caspase-3表达水平。结果与IR组比较,M、B、D组上述指标下调(P<0.05);与D组比较,M、B组caspase-3浓度、AI、血清cTnI浓度上调,差异均有统计学意义(P<0.05)。结论 GSK-3β与Drp-1在大鼠心肌保护作用中并非单一依赖关系。

Objective To investigate the relationship between GSK-3β and Drp-1 in the myocardium protection in rats.Methods 60 healthy male SD rats,weighing 250-300 g,randomly divided into 4 groups（n =15）：Ischemia reperfusion group（group IR）,Ischemia reperfusion ＋Mivi-1 treatment group（group M）,Ischemia reperfusion ＋SB216763 treatment group（group B）,and Ischemia reperfusion＋Mivi-1 treatment group＋SB216763 treatment group（group D）.The myocardial ischemia-reperfusion injury model was established by ligating the LAD for 30 min and reperfusion for 120 min.Mdivi-1（1.2 mg/kg） was given at 1 min before reperfusion in group M by intravenous injection.SB216763（0.2 mg/kg） was given at 1 min before reperfusion in group B by intravenous injection.Both of them were given at 1 min before reperfusion in group D by intravenous injection.cTnI concentration was detected from abdominal aorta blood.Myocardial specimens were obtained from the apex for determination of the AI by TUNEL.Myocardial pathology were observed and the expression of caspase-3 was detected by Western blot.Results Compared with IR group,the levels of caspase-3,AI and myocardial injury in M,B and D groups were down-regulated（P〈0.05）.Compared with D group,the levels of caspase-3,AI and myocardial injury were increased in M and B group the differences were statistical significant（P〈0.05）.Conclusion The relationship between GSK-3β and Drp-1 of the myocardium protection in rats is not a single dependency.