褪黑素对大鼠肝缺血再灌注损伤的保护作用研究

The protective effects of melatonin on hepatic ischemia-reperfusion injury in rats

目的探讨褪黑素(MT)对大鼠肝脏缺血再灌注损伤的保护作用及其作用机制。方法成年Wister大鼠60只分为假手术组、手术对照组、手术+VitC组(125mg4kg)、手术+MT1组(0.2mg4kg)、手术+MT2组(1mg4kg)、手术+MT3组(5mg4kg)。测定各组大鼠肝缺血40min再灌注90min后血清中ALT、AST水平和肝组织中的丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)含量,电镜观察肝细胞线粒体的结构变化。结果与对照组相比,MT组血清ALT和AST值上升幅度明显降低(均P<0.01);MT组的肝组织中MDA含量显著降低,SOD、CAT的含量明显提高(P<0.01);MT组肝组织HE染色光镜观察肝小叶结构保存较完整,肝细胞肿胀减轻;电镜观察肝细胞线粒体结构保存较完整。结论MT对大鼠肝缺血再灌注致肝损伤具有保护作用。其保护机制可能是通过维持肝组织内SOD、CAT含量,清除氧自由基,抗脂质过氧化,稳定细胞膜性结构来实现的。

Objective To investigate the protective effect of MT on hepatic ischemia/ reperfusion （I/ R） injury in rats. Methods Sixty rats were randomly divided into six groups： nonischemic controls, ischemia reperfusion group, VitC treatment group （125mg/kg）, and three melatonin treatment groups： MT1 （0.2mg/kg）, MT2 （lmg/kg） and MT3 （5mg/kg）. The marker enzymes of liver damage （ALT,AST）, malondialdehyde （MDA）, and activities of superoxide dismutase （SOD）, catalase （CAT） were measured in all 6 groups. Electron microscope was used to observe ultrastructure changes of hepatocytes. Results After 40 min ischemia and 90 min reperfusion, the contents of ALT, AST and MDA were significantly elevated, SOD, CAT activities declined. But in MT treatment group, the contents of ALT, AST and MDA were significantly lower; SOD, CAT activities were higher than those in I/R group （P〈0.01）. Compared with I/R group, mitochondria swelling was less marked and no break of crest and the tunica was observed in the MT group. Conclusion MT can protect the liver from I/R injury, which may be associated with its anti-oxidase function and maintaining the membrane construction of mitochondria.