自由基及N-乙酰半胱氨酸在鼠肝超急性排斥反应中的作用

Role of reactive species and N-acetylcysteine in hyperacute rejection of the rats liver in the isolated perfusion model

目的 研究自由基在异种移植超急性排斥反应 (HAR)中的作用。方法 2 4只SD大鼠分为 4组 ,同种组、异种组、N 乙酰半胱氨酸 (NAC)治疗的同种组和异种组。全麻下分离出大鼠的胆总管、门静脉、肝上下腔静脉并插管 ,缺血 3 0min后灌注鼠肝 2h ,按每 3 0min收集胆汁 ,监测灌注压力并取血检测脂质超氧化 (MDA)、氮自由基 (NO)、肝功能。结果 异种组MDA、NO和灌注压及肝功能均明显高于同种组 ,胆汁量低于同种组 ;NAC的治疗抑制了异种组MDA、NO、肝功能及灌注压的升高 ,增加了胆汁量 ,对同种组无明显作用。结论 自由基在鼠肝的HAR中可能起重要作用 ,NAC的治疗可部分抑制HAR。

Objective To evaluate the effect of reactive species in hyperacute rejection (HAR) and the ability of N-acetylcysteine (NAC) in reducing HAR of the rat livers.Methods Twenty-four Sprague-Dawley (SD) rats were divided into 4 groups:isogenic group,xenogenic group,NAC-treated isogenic group and NAC-treated xenogenic group.Under general anesthesia the common bile duct,portal vein and suprahepatic vena cava were dissected and cannulated respectively.After the infrahepatic vena cava was ligated,the liver was flushed in situ through portal vein with cold Ringer solution.Thirty-min ischemia and a subsequent 120-min reperfusion was induced in an in situ isolated perfusion model of the rat liver.The blood samples were collected at different time points for the measurement of lipid peroxidation (MDA),RNS (nitrite and nitrate),and liver enzymes (ALT,AST,LDH,ALP).During the reperfusion,the perfusion pressure was monitored and the bile volume was collectedevery 30 min.Results In xenoperfused group the lipid peroxidation,nitric radicals and ALT,AST,LDH and perfusion pressure were significantly higher than the isogenic group.The bile volume was significantly reduced inxenogenic group.The addition of NAC could reduce the concentration of MDA,nitric radicals,liver tissue MDA and the perfusion pressure in xenogenic group.NAC also prevented the significant increase of ALT,AST,LDH and improved the bile volume in the same group.Conclusion The mechanism of HAR is different from reperfusion injury.Reactive species might be involved in HAR.NAC is able to reduce both RNS and lipid peroxidation and improves the function of xenoperfused liver significantly.