缺血后处理对缺血-再灌注心肌的保护作用及其与线粒体ATP敏感性钾通道的关系

目的探讨缺血后处理（IPo）的心肌保护作用及与心肌线粒体三磷酸腺苷（ATP）敏感性钾通道（mitoKATP）的关系,为药物后处理的研发提供依据。方法40只Wistar大鼠,建立大鼠离体心脏Langendorff灌注模型,采用随机数字表法分为5组,每组8只,正常对照组（NC组）：用K-H液持续灌注100min,不做任何处理;缺血-再灌注（I/R）组：全心缺血40min,再灌注60min;IPo组：全心缺血40min,再灌注10s,缺血10s,反复6次,然后持续再灌注58min;5-羟基癸酸（5-HD）组：全心缺血40min后,先用含5-HD（100μmol/L）的K-H液再灌注15min,再用不含5-HD的K-H液再灌注45min;IPo＋5-HD组：全心缺血40min后,先用含5-HD（100μmol/L）的K-H液再灌注10s,缺血10s,反复6次,再用含5-HD的K-H液持续灌注13min,然后用不含5-HD的K-H液再灌注45min。观察比较各组心功能、冠状动脉流量（CF）、冠状动脉流出液中心肌肌钙蛋白I（cTnI）含量、心肌梗死（AMI）面积和心肌细胞超微结构改变。结果再灌注末IPo组左心室发展压（74.3±3.3mmHgvs.57.1±3.3mmHg,t=13.00,P=0.000）、＋dp/dtmax（1706.6±135.6mmHg/svs.1313.3±96.2mmHg/s,t=6.28,P=0.000）、-dp/dtmax（1132.8±112.1mmHg/svs.575.7±67.7mmHg/s,t=13.48,P=0.000）、CF（6.49±0.30ml/minvs.3.70±0.24ml/min,t=28.60,P=0.000）与I/R组比较均升高;左心室舒张期末内压（10.9±1.7mmHgvs.26.2±1.5mmHg,t=-19.21,P=0.000）,冠状动脉流出液中cTnI含量（0.62±0.01ng/mlvs.0.71±0.01ng/ml,t=-12.00,P=0.000）均降低,AMI面积与I/R组比较减少20.8%（P〈0.05）。IPo＋5-HD组对心肌的保护作用与IPo组相似,但作用轻于IPo组。电子显微镜观察结果表明,IPo和IPo＋5-HD可减轻I/R引起的心肌纤维和线粒体损伤。结论IPo对I/R心肌有保护作用,其作用与mitoKATP的激活有关。

The Protective Effects of Ischemic Post-conditioning on Ischemia-reperfusion Myocardium and the Relationship with Mitochondrial Adenosine Triphosphate Sensitive K+ Channels

Objective To investigate the protective effects of ischemic post-conditioning （IPo） on ischemia-reperfusion （I/R） myocardium and the relationship with mitochondrial adenosine triphosphate （ATP） sensitive K^＋ channels （mitoKATP） and provide evidences to the development of drug-induced post-conditioning. Methods Langendorff models were established in 40 Wistar rats which were divided into 5 groups by random number table with 8 rats in each group. Normal control group（NC group）：the rat hearts were continuously reperfused by Krebs-Henseleit bicarbonate buffer （K-HB） for 100 min without any other treatment; I/R group：the rat hearts underwent a 40-min global ischemia followed by a 60-min reperfusion; IPo group：after a 40-min global ischemia,the process of 10-second reperfusion followed by a 10-second ischemia was repeated 6 times,then there was a continuous 58-min reperfusion; 5-hydroxydecanoic acid（5-HD） group：after a 40-min global ischemia,hearts with 5-HD（100 μmol/L） K-HB were reperfused for 15-min and then perfused without 5-HD for 45-min;IPo＋5-HD group：after a 40-min global ischemia,the process that the isolated hearts with 5-HD（100 μmol/L） K-HB were reperfused for 10-second followed by a 10-second ischemia was repeated 6 times,then the hearts with 5-HD（100 μmol/L） K-HB were continuously perfused for 13-min followed by reperfusion without 5-HD（100 μmol/L） K-HB for 45-min. The cardiac function,coronary flow（CF）,cardiac troponin I（cTnI） content in coronary effluent,the area of acute myocardial infarction （AMI） and myocardial ultrastructure were observed. Results Left ventricular developed pressure（74.3±3.3 mm Hg vs. 57.1±3.3 mm Hg,t=13.00,P=0.000）,＋dp/dtmax（1 706.6±135.6 mm Hg/s vs. 1 313.3±96.2 mm Hg/s,t=6.28,P=0.000）,-dp/dtmax（1 132.8±112.1 mm Hg/s vs. 575.7±67.7 mm Hg/s,t=13.48,P=0.000） and CF（6.49±0.30 ml/min vs. 3.70±0.24 ml/min,t=28.6,P=0.000） in IPo group were higher than those in I/R group. Left ventricular en