线粒体KATP通道在脑啡肽预处理体外循环心肌保护中的作用  

Role of mitochontrial KATP channel in opiold cartlioprotection after ischemia-reperfusion during cartliopulmonary bypass

作　　者：卢蓉[1] 范慧敏[1] 洪暄[1] 刘中民[1] 

机构地区：[1]同济大学附属东方医院心胸外科中德心脏中心,上海200120

出　　处：《中华胸心血管外科杂志》2008年第3期185-187,共3页Chinese Journal of Thoracic and Cardiovascular Surgery

基　　金：本课题受国家自然科学基金资助（30371417）

摘　　要：目的通过建立猪体外循环（CPB）心肌缺血再灌注（MI／R）模型对δ阿片受体介导的CPBMI／R损伤早期时相的心肌保护效果、作用机制以及线粒体KATP通道的角色进行探讨，以期为临床心肌保护提供理论和实验依据。方法24只成年家猪（30～35kg）随机分为对照组（C组）、δ阿片样受体激动剂脑啡肽组（D组）和脑啡肽＋线粒体KATP通道阻滞剂组（D＋K组），每组8只，常规建立CPB模型，主动脉阻断同时灌注改良St．qlaomas停搏液。每组于CPB前、主动脉开放时、CPB结束时、停机后1、2h检测冠状静脉窦血肌钙蛋白（TnT）含量，相应时间点监测左室收缩压（LVSP），左室舒张末期压（LVEDP）和左室内压最大变化速率（±dp/dtmax），分别于CPB前和停机后2h取左心室心肌，作心肌组织Gia蛋白的表达、PKC的表达和ATP含量的测定。并应用透射电镜观察心肌再灌注损伤超微结构的变化。结果（1）D组的心功能改变明显优于C和D＋K组。（2）C和D＋K组TnT的升高比D组明显。（3）D组心肌ATP含量较C和D＋K组高。（4）透射电镜下C和D＋K组呈现出明显的MI／R损伤表现，而D组的心肌超微结构损伤较轻。（5）和C和D＋K组以及正常心肌相比，D组Gin蛋白和PKC的表达更为明显。结论（1）CPB前1h应用一次δ阿片受体激动剂脑啡肽（DADLE）能产生明显的早期时相心肌保护作用。（2）Gi蛋白-PKC．线粒体KATP通道途径是δ阿片受体介导的猪CPB MI／R损伤早期时相心肌保护中一条重要的信号传导途径。Objective By establishing the swine cardiopulmonary bypass（CPB） myocardial ischemia-reperfusion （MI/R） model, the early phase card/oprotective effects and the role of the mitochondrial KATP channel were studied to provide basic and experimental evidences for clinical eard-ioprotection. Methods 24 adult swines（30-35 kg） were randomly divided into 3 groups：group C（control group, n=8）, group D（using δ-opiold agonist-DADLE, n = 8） and group D＋ K （using DADLE and Glibenclamide, n= 8）. CPB was instituted routinely and the improved St. Thomas cold cardioplegic solution was administered into the root of aorta. Blood samples were taken from coronary, sinus before CPB, beginning of reperfusion, the end of CPB, one hour after CPB, two hours after CPB to measure TnT. The LVSP, LVEDP and ＋ dp/dtmax were measured at the corresponding time points. Specimens of the left ventricular myocardinm were taken before CPB and two hours after CPB for the expressions of Gin protein and PKC, the values of ATP. And the cardium ultrastmetures were observed. Results （ 1 ） Parameters of cardiac function in group D were found obviously better than those in grooup C and D ＋ K. （2）Concentrations of TnT increased obviously in group C and D ＋ K compared with group D. （3）The values of ATP in Group D were obviously higher than those in group C and D＋ K. （4）Group D showed slight injuries in electron microscopy than those in group C and D ＋ K. （5）The expressions of Gin protein and PKC in group D were obviously higher than those in group C, group D ＋ K and nonpreconditioned myocardium. Conclusion （1）δ-opioid receptor agonist DADLE could induce the early phase cardioprotection after CPB in swine. （2）Gi-PKC-Mitochondrial KATP Channel is an important signaling pathway in the early phase cardioprotectinn.

关 键 词：线粒体KATP通道 心肌保护效果 体外循环 脑啡肽 心肌缺血再灌注 阿片受体激动剂 预处理 透射电镜观察 

分 类 号：R686[医药卫生—骨科学]