ATP敏感性钾通道在七氟醚预处理延迟相减轻大鼠心肌缺血-再灌注损伤中的作用

Role of mitochondrial ATP sensitive potassium channel in delayed preconditioning with sevoflurane reducing myocardial ischemia-reperfusion injury in rats

目的探讨线粒体ATP敏感性钾通道(mito-KATP)在七氟醚预处理延迟相减轻大鼠心肌缺血-再灌注(I-R)损伤中的作用。方法雄性SD大鼠80只随机均分为五组:假手术组(A组);I-R组(B组),左冠状动脉前降支结扎30min后再灌注120min;七氟醚预处理组(C组),I-R前24h吸入2.5%七氟醚1h;七氟醚预处理+mito-KATP抑制剂5-羟基癸酸(5-HD)组(D组),七氟醚预处理前尾静脉注射5-HD5mg/kg;单纯5-HD组(E组)。再灌注120min后各组取10只大鼠测定心肌缺血危险面积与梗死面积,酶联免疫吸附(ELISA)法检测血清肌钙蛋白I(cTnI)浓度,各组另取6只大鼠采用免疫印迹检测左室心肌Bcl-2及Bax蛋白表达。结果七氟醚预处理可减少I-R引起的心肌梗死面积、降低血清cTnI水平,上调心肌Bcl-2表达、下调Bax表达(P<0.05)。而这种效应可以被5-HD所抑制。结论七氟醚预处理延迟相可减轻大鼠心肌I-R损伤,可能与mito-KATP开放引起的Bcl-2及Bax表达变化有关。

Objective To investigate the role of mitoehondrial ATP sensitive potassium clmnnel （mito- KATP） in the delayed cardioprotection produced by sevoflurane in ischemia-reperfusion（I-R） injured rats. Methods Eighty male Sprague-Dawley rats were randomly divided into five groups： a sham operation group （group A）; an ischemia-repeffusion injury group （group B）, occlusion of left anterior descending coronary artery for 30 min and followed by 120min of repeffusion; a sevoflurane preconditioning group （group C）, breathing 2. 5% sevoflurane for one hour 24 h before IR; a sevoflutane preconditioning＋5 hydroxydecanoate （5 HD, a mito-KATP inhibitor） group （group D）, 5 liD 5mg/kg was given before sevoflurane preconditioning; and a 5 HD group （group E）. After 120 min of repeffusion, myocardial area at risk in ischemia and infarcted size （IS） were measured by double stain with evans blue and TTC. Serum cTnI levels were detected with EIdSA. The expression of Bob2 and Bax was measured with immunoblotting. Results Preconditioning with sevoflurane decreased the IS induced by LR, reduced eTnI level, upregulated Bcl-2 protein and dowuregulated Bax expression （all P〈0. 05）, but this effect was inhibited by 5 HD. Conclusion Delayed preconditioning with sevoflurane protects myocardial ischonia-reperfusion injury by regulating Bcl-2 and Bax expression that may be associated with mito-KATp channel aetivation.