尼可地尔后处理对大鼠肺缺血再灌注损伤的保护作用

摘要

Objective To discuss the function and possible mechanism of nicorandil postconditioning in the mitigation of rat's lung ischemia-reperfusion injury( LIRI ) as mitoKATP opener. Methods The model of rat's LIRI was established. Fifty rats were averagely divided into five groups at randomly: sham operation group, IRI group, IPO group, nicorandil(Nic ) group and combination group of nicorandil and 5-hydroxydecanoate. The level of malondial-dehyde( MDA ), superoxide Dismutase( SOD ), and the ratio of W/D were tested in each group. Meanwhile, lung tissue cell apoptotic index( AI ) was tested with TdT-mediated dUTP-biotin nick end labeling( TUNEL ) and the expression level of Caspase-3 in lung tissue was determined with immunohistochemistry staining. Lung pathomorpho-logical observation was performed with light and electron microscope. Results The level of MDA, AI, ratio of W/ D, and expression of Caspase-3 were increased significantly, while the activity of SOD was decreased in IRI and combination group of nicorandil and 5-hydroxydecanoate, compared with sham group( P <0. 05 ); but the opposite situation was observed when compared with IPO and Nic groups( P < 0. 05 ); no significant difference was found between IRI and combination group of nicorandil and 5-hydroxydecanoate. The same result was found between IPO and Nic groups. Conclusion LIRI is alleviated by nicorandil through simulating IPO protective mechanism, which may include opened mitoKATP, decreased MDA, increased SOD and downregulated Caspase-3.%目的 探讨线粒体ATP敏感性钾通道(mitoKATP)开放剂尼可地尔后处理在减轻大鼠在体肺缺血再灌注损伤(LIRI)的作用及其可能的机制.方法 建立大鼠在体LIRI模型,将50只SD大鼠随机均分为5组:假手术组(Sham组)、缺血再灌注损伤组(I/R组)、缺血后处理组(IPO组)、尼可地尔(Nicorandil)后处理组(Nic组)及尼可地尔+5-羟基葵酸(5-HD)后处理组(Nic+5-HD组).检测各组肺组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、湿/干比值(W/D);原位缺口末端标记(TUNEL)测定肺组织细胞的凋亡指数(AI);免疫组化染色法检测肺组织半胱氨酸天冬氨酸特异性蛋白酶-3(Caspase-3)的表达;光镜及电镜观察肺组织的病理形态学变化.结果 与Sham组比较,I/R组和Nic+5-HD组肺组织MDA含量明显增加、SOD活性显著降低、W/D明显升高、AI明显增大、Caspase-3的表达明显增加(P<0.05);与I/R组和Nic+5-HD组比较IPO组和Nic组肺组织MDA含量明显减少、SOD活性显著增高、W/D明显降低、AI明显减小、Caspase-3的表达明显降低(P<0.05);I/R组各指标与Nic+5-HD组、IPO组各指标与Nic组比较差异无统计学意义.结论 尼可地尔后处理可以通过模拟缺血后处理减轻LIRI,其肺保护的机制可能涉及mitoKATP开放,使MDA含量减少、SOD活性增高、下调Caspase-3的表达有关.