阿片受体对体外循环缺血再灌注损伤心肌的保护作用  

Role of opioid receptor in cardioprotection after ischemia-reperfusion during cardiopulmonary bypass

作　　者：刘中民[1] 洪暄[1] 范慧敏[1] 卢蓉[1] 

机构地区：[1]同济大学附属东方医院心胸外科, 上海200120

出　　处：《中华胸心血管外科杂志》2008年第4期258-261,共4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（MVR）模型对δ阿片受体激动剂脑腓肽（DADLE）介导的CPBMI／R损伤早期时相和后时相的心肌保护作用进行探讨，以期为临床心肌保护提供理论和实验依据。方法将2，4只成年家猪随机分为对照组、早期时相和后时相组，每组8只常规建立CPB模型，主动脉阻断同时灌注改良St．Thomas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舒张末期压（LVEDP）和左室内压最大变化速率（±dp/dtmax），于停机后2h取左心室心肌，进行心肌组织Gin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）和早期时相和后时相组相比，对照组心功能指标明显下降。（2）对照组的TnT较早期时相和后时相组明显升高，ATP含量明显降低。（3）和对照组相比，早期时相和后时相组Gin蛋白和PKC的表达更为明显。（4）透射电镜下早期时相和后时相组的心肌超微结构损伤均较对照组明显轻微。结论（1）和CPB前1h应用一次DADLE而产生的早期时相心肌保护作用相比，CPB前48h和24h两次应用DADLE引发的后时相心肌保护作用更为显著。（2）Gi蛋白-PKC途径可能是δ阿片受体介导的猪CPB MI／R损伤心肌保护中一条重要的信号传导途径。Objcetive By establishing the swine cartliopulmonary bypass（CPB） myocardial ischemia-reperfusion （MI/R） model, the early phase and the late phase cardioprotective effects of 8-opioid receptor agonist DADDLE were studied to provide academic and experimental evidences for clinical cardioprotection. Methods 24 adult swines were randomly divided into 3 groups： control group（n= 8）, early phase cardioprotection group（n= 8） and late phase cardioprotection group（n= 8）. CPB was instituted routinely and the modified St. Thomas cold cardioplegic solution was administered int. 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 afar CPB to measure TnT. The LVEDP and ±dp/dtmax were measured at the corresponding time points. Specimens of the left ventricular myocardium were taken before CPB and two hours after CPB for the expressions of Gia protein and PKC, the values of ATP. And the myocardium ultrastructures were observed. Results （1） Parameters of cardiac fimction in control group were found decreased significantly than those in early and late phase cardioprotection groups. （2） Concentrations of TnT increased significantly in control group compared with early and late phase cardioprotection groups. The values of ATP decreased significantly in control group. （3）The expressions of Gia protein and PKC in early and late phase eardioprotection groups were significantly higher than those in control group and nonpreconditioned myocardium. （4）Early and late plase cardioprotection groups showed milder injuries in electron microscopy than those in control group. （1）Compared with the early phase eardioprotection induced by δ-opioid receptor agonist DADLE after CPB in swine,the late phase cardioprotection has more advantages. （2）Gi-PKC might be an important signaling pathway in the δ-opioid receptor induced cardioprotection.

关 键 词：受体  阿片样 心肺转流术 心肌再灌注损伤 心肌保护 

分 类 号：R686[医药卫生—骨科学]