吗啡延迟预处理对兔心肌缺血再灌注损伤p38丝裂原活化蛋白激酶的影响

目的探讨吗啡延迟预处理对兔心肌缺血再灌注损伤的保护机制。方法 30只健康新西兰雄性大白兔随机分成3组：假手术组（C组）、缺血再灌注组（I/R组）、吗啡预处理组（M组）,每组10只。C组仅行左冠状动脉套线而不阻断160min;I/R组行左冠状动脉阻断40min,再灌注120min;M组在静注吗啡1.0mg/kg24h后处理同I/R组。各组分别于左冠状动脉前降支阻断前20min（T1）、左冠状动脉前降支阻断20min（T2）、左冠状动脉前降支阻断40min（T3）、心肌再灌注1h（T4）、心肌再灌注2h（T5）5个时点抽取颈内动脉血测定血清中TNF-α含量。再灌注120min后,免疫印迹法测心肌p38丝裂原活化蛋白激酶（P38MAPK）活性水平,同时测心肌梗死面积。结果与I/R组比,M组TNF-α含量降低,p38MAPK活性降低,心肌梗死面积减少[M组（21.5%±2.4）%,I/R组（37.8%±1.7）%]。上述差异均有统计学意义（均P〈0.05）。结论吗啡延迟预处理对心肌缺血再灌注损伤的保护作用可能通过抑制心肌p38MAPK的活性、减少TNF-α生成来实现。

Effects of Morphine Delayed Preconditioning on p38MAPK During Myocardial Ischemia Reperfusion Injury in Rabbits

Objective To investigate the protective effects of morphine-delayed preconditioning on myocardial ischemia reperfusion（I/R） injury and the potential mechanisms in rabbit.Methods Thirty New Zealand male white rabbits were randomly assigned to 3 groups：（1） the control group（group C）,（2） I/R group（group I/R）,（3） morphine group（group M）.Group C and group I/R were given NS served as the untreated controls.Group M was given morphine 1.0 mg/kg before myocardial ischemia.Twenty-four hours later group I/R and group M underwent 40 min of coronary occlusion followed by 2 h of reperfusion.Blood samples were taken from arterial line 20 min before occlusion（T1）,20 min after occlusion（T2）,40 min after occlusion（T3）,1 h after reperfusion（T4） and 2 h after reperfusion（T5） for determination of the plasma levels of TNF-α.At the end of the reperfusion,infarct size and area at risk were defined by Evans and TTC staining.The heart was harvested and levels of the p38MAPK activity were determined by Western blot analysis and ultrastructures were observed by electron microscopy.Results The p38MAPK activity of group M was lowered than that in the group I/R（P0.05）.Morphine significantly（P0.05） reduced infarct size[（21.5%±2.4）% in group M] of the left ventricular area at risk significantly as compared with the controls [（37.8%±1.7）% in group I/R].Group M had a lower level of TNF-α than that in the group I/R.Conclusion Morphine can inhibit p38MAPK activity during myocardial ischemia reperfusion and modulate the level of TNF-α,which may be one of the molecular mechanisms of morphine-delayed preconditioning on cardioprotection.