mitoKATP通道在瑞舒伐他汀联合缺血后处理减轻糖尿病大鼠心肌缺血再灌注损伤中的作用

目的观察瑞舒伐他汀后处理联合缺血后处理是否能减轻2型糖尿病大鼠缺血再灌注损伤并探讨其相应机制。方法建立2型糖尿病大鼠模型,并随机分成7组(每组9只):假手术组、缺血再灌注损伤组(IRI组)、瑞舒伐他汀后处理+缺血后处理组(RPO+IPO组)、瑞舒伐他汀后处理+缺血后处理组+5-羟基喹酸盐组(5-HD组)、瑞舒伐他汀后处理+缺血后处理组+二氮嗪组(二氮嗪组)、瑞舒伐他汀后处理+缺血后处理组+HMR-1098组(HMR-1098组)、瑞舒伐他汀后处理+缺血后处理组+克罗卡林组(克罗卡林组)。进行45 min缺血和120 min再灌注,观察心肌梗死区面积及心肌细胞线粒体超微结构和血清心肌肌钙蛋白T水平。结果 RPO+IPO组、二氮嗪组、HMR-1098组和克罗卡林组心肌梗死面积较IRI组明显减小(P<0.05),5-HD组心肌梗死面积明显大于RPO+IPO组、二氮嗪组、HMR-1098组及克罗卡林组(P<0.05)。IRI组和5-HD组心肌细胞线粒体超微结构损伤重,RPO+IPO组、二氮嗪组、HMR-1098组及克罗卡林组心肌细胞线粒体超微结构基本完整。RPO+IPO组、二氮嗪组、HMR-1098组及克罗卡林组血清心肌肌钙蛋白T水平较IRI组明显减少(P<0.05),5-HD组血清心肌肌钙蛋白T水平与IRI组无明显差异,但明显高于RPO+IPO组、二氮嗪组、HMR-1098组及克罗卡林组(P<0.05)。结论瑞舒伐他汀后处理联合缺血后处理可明显减轻2型糖尿病大鼠缺血再灌注损伤,mitoKATP通道开放在此作用中起主导地位。

Role of mitoKATP Channel in the Combination of Rosuvastatin and Ischemic Postcondition on Myocardium Against T2DM Rats Ischemia-Reperfusion Injury

Aim To observe whether rosuvastatin postconditioning(RPO) and ischemic postconditioning(IPO) could attenuate ischemia-reperfusion injury(IRI) in T2DM rats,and to investigate the potential cardioprotective mechanisms involved. Methods Induced by streptozotocin plus nicotinamide,a T2DM rat model was successfully created in 54 healthy Wistar male rats,which were randomly allocated into seven groups(n=9): Sham group,IRI group,RPO+IPO group,5-HD group,diazoxide group,HMR-1098 group,and Cromakalim group.Infarct size,ultrastructure,serum cTnT were determined at the end of ischemia-reperfusion,which underwent 45 min ischemia and 120 min reperfusion. Results Compared with IRI group,the myocardial infarct size significantly decreased in RPO+IPO group and diazoxide group,HMR-1098 group,Cromakalim group(P<0.05).The myocardial infarct size in 5-HD group significantly increased than that in RPO group and diazoxide group,HMR-1098 group,and Cromakalim group(P<0.05).TEM revealed that the myocardial cell mitochondria ultrastmctural damages were serious in IRI group and 5-HD group.In RPO+IPO group,diazoxide group,HMR-1098 group and Cromakalim group,the structure of most mitochondria maintained as originally on the whole.As compared with IRI group,the level of cTnT in RPO+IPO group and diazoxide group,HMR1098 group,Cromakalim group was significantly reduced(P<0.05).The level of cTnT in 5-HD group was significantly increased than that in RPO+IPO group and diazoxide group,HMR-1098 group,Cromakalim group(P<0.05). Conclusions RPO+IPO could significantly attenuate IRI in vivo T2DM rats.mitoKATP channel but not sarcKATP channel plays the major role in the protection effects of rosuvastatin postconditioning.