右美托咪定预处理减轻离体大鼠心脏缺血/再灌注损伤的线粒体相关机制

Dexmedetomidine preconditioning protects isolated rat hearts against ischemia/reperfusion injuries and its mechanism

目的:研究右美托咪定(dexmedetomidine,Dex)预处理对心肌缺血/再灌注(I/R)损伤的作用及其与线粒体渗透性转换孔(mPTP)和/或线粒体ATP敏感性钾通道(mitoKATP)的关系。方法:分离SD雄性大鼠心脏置于Langendorff系统行全心停灌30 min,再灌注120 min建立心肌I/R损伤模型,停灌前15 min给予Dex(10 nmol/L)处理。测定左心室动力学、再灌注期间冠脉流量及再灌注5 min时中乳酸脱氢酶(LDH)含量,实验结束测定心肌组织formazan含量以反映心肌梗死状况。结果:与正常对照组相比,I/R组明显降低了再灌注期间的左室发展压、冠脉流量及再灌注末心肌组织formazan含量,显著升高了再灌注左室舒张末压、心肌LDH渗出;Dex预处理明显改善了I/R心脏功能及心肌组织活性(P<0.01);mPTP开放剂苍术苷(20μmol/L,再灌注前给药20min)及mitoKATP抑制剂5-羟基癸酸(100μmol/L,停灌前给药20 min)可取消Dex预处理产生的抗心脏I/R损伤作用。结论:围手术期常用的辅助麻醉药Dex具有减轻离体大鼠心脏I/R损伤作用,且该心肌保护作用可能与Dex促进缺血前mitoKATP的开放,抑制再灌注早期mPTP的开放有关。

Objective： To investigate the protective effect of dexmedetomidine（Dex） preconditioning against ischemia/reperfusion（I/R） injuries in isolated rat hearts and its relation to mitochondrial permeability transition pore（mPTP） and mitochondrial ATP-sensitive K＋ channel（mitoKATP）.Methods： The hearts of male SD rats were isolated to mount on the Langendorff apparatus and subjected to 30 min global ischemia followed by 120 min reperfusion.The isolated hearts were treated with Dex（10 nmol/L） before ischemia for 15 min.The left ventricular hemodynamic parameters,coronary flow（CF） and the lactate dehydrogenase（LDH） release in the coronary effluent at 5 min reperfusion were measured.The formazan content was assayed to determine the myocardial viability at the end of reperfusion.Results： Compared with normal controls,I/R markedly decreased the left ventricular developed pressure and CF during the whole reperfusion period and the formazan content;while the left ventricular end diastolic pressure and LDH release were significantly increased.Dex preconditioning markedly improved the myocardial viability and cardiac function（P0.01）,which were reversed by the treatment with both atractyloside（20 μmol/L before ischemian）,an opener of mPTP,and 5-hydroxydecanoate（100 μmol/L at the beginning of reperfusion）,an inhibitor of mitoKATP,for 20 min.Conclusion： Dex has protective effect against I/R injuries in isolated rat hearts,which may be related to inhibiting the opening of mPTP at the beginning of reperfusion and activating mitoKATP before ischemia.