吗啡预处理-后处理对大鼠离体心脏缺血再灌注损伤的影响

Effects of morphine preconditioning-postconditioning on ischemia-reperfusion injury in isolated rat hearts

目的探讨吗啡预处理-后处理对大鼠离体心脏缺血再灌注损伤的影响。方法雄性SD大鼠，体重180～200g，应用Langendofff体外灌流装置，采用全心停灌45min、再灌注60min的方法制备大鼠离体心脏缺血再灌注模型。取模型制备成功的心脏40个，随机分为5组（n=8）：缺血再灌注组（IR组）、吗啡预处理组（M1组）、吗啡后处理组（M2组）、吗啡预处理-后处理组（M1＋M2组）、5-羟葵酸（5-HD）混合吗啡后处理组（5-HD＋M2组）。M1组全心停灌前30min灌注含3．0μmol／L吗啡的K—H液20min，随后灌注K—H液10min。M2组再灌注即刻灌注含3．0μmol／L吗啡的K—H液10min，随后灌注正常K—H液50min。5-HD＋M2组再灌注即刻灌注含3．0μmol／L吗啡＋10^-4mmol/L 5-HD的K-H液10min，随后灌注正常K—H液50min。于再灌注60min时，测定心肌肌酸激酶（CK—MB）活性，计算心肌梗死区与缺血危险区的比值（IS／AAR）。结果与IR组相比，其余各组IS／AAR减少，CK-MB活性降低（P〈0．05）；与M，组比较，5-HD＋M2组CK—MB活性及IS／AAR升高（P〈0．05）；M1组、M2组和M1＋M2组上述指标比较差异无统计学意义（P〉0．05）。结论吗啡预处理．后处理虽然可减轻大鼠离体心脏缺血再灌注损伤，但是与单独应用时效果相似，其原因可能是两者单独应用减轻心脏缺血再灌注损伤的机制均与开放线粒体ATP敏感性钾通道有关。

Objective To evaluate the effects of morphine preconditioning-postconditioning on isehemiarepeffusion （I/R） injury in isolated rat hearts. Methods Male SD rats weighing 180-200 g were killed after intraperitoneal injection of heparin 500 U/kg. The hearts were immediately removed and peffused in a Langendorff apparatus with K-H solution gassed with 95 % O2-5 % CO2 . HR and left ventricular systolic pressure （LVSP） were measured from a fluid-filled latex balloon in the left ventricle. Global myocardial ischemia was induced by interrupting peffusion for 45 min followed by 60 min reperfusion. Forty isolated rat hearts were randomly divided into 5 groups （ n = 8 each） ： group Ⅰ （I/R）; group Ⅱ morphine preconditioning （M1） ; group Ⅲ morphine postconditioning （M2）; group Ⅳ M1 ＋ M2 ; group Ⅴ 5-hydroxydecanoate （5-HD） ＋ M2 . Group M, was peffused with K-H solution containing morphine 3.0 μmol/L tot 20 min 30 min before ischemia followed by 10 min normal K-H solution perfusion. Group M2 was perfused with K-H solution containing morphine 3.0 μmol/L for 10 rain at the beginning of repeffusion followed by 50 min nonnal K-H solution perfusion. Group 5-HD ＋ M2 was perfused with K-H solution containing morphine 3.0 μmol/L ＋ 5-HD 10^-4 mmol/L for 10 min at the beginning of reperfusion followed by 50 min normal K-H solution perfusion. Myocardial CK-MB activity was measured and myocardial infarct size （IS/AAR） determined （by 2,3,5-triphenyl tetrazolium staining） at the end of 60 min reperfusion. Results The preconditioning, postconditioning and combination of preconditioning and postconditioning with morphine 3.0μmol/L perfusion for 10 min all provided cardio-protective effects in terms of IS/AAR and myocardial activation of CK-MB. Conclusion Although tile combination of morphine preconditioning and postconditioning can protect the heart against I/R injury, the effects are similar to those of either of them alone, and the reason may be that either of them alone protects the heart against I/R injury, via activating mitoKATP.