大鼠肾移植急性排斥反应中诱导型一氧化氮合酶的表达及其抑制剂的作用

目的:探讨大鼠移植肾组织中诱导型一氧化氮合酶(iNOS)的表达及iNOS抑制药氨基胍(Aminoguanidine,AG)和免疫抑制药他克莫司(FK506)对移植术后急性排斥反应的影响。方法:实验分为同基因移植组(5只,供、受鼠均为SD大鼠)和异基因移植组,后者又分为急性排斥组、AG治疗组和他克莫司治疗组(各组大鼠均为5只,供鼠为SD大鼠,受鼠为Wistar大鼠)。术后第7 d取移植物进行病理检查,观察排斥反应发生情况,并运用RT-PCR、免疫组化法检测各组移植肾组织中iNOS的表达水平。结果:急性排斥组iNOS表达呈强阳性,与AG治疗组、他克莫司治疗组、同基因移植组比较,差异有显著性意义(P<0.01)。AG治疗组、他克莫司治疗组、同基因移植组之间比较,差异无显著性意义。结论:在大鼠原位肾移植发生急性排斥反应时,iNOS表达明显增高,增高程度与排斥反应的强度移植物损伤有明显关系。应用AG和他克莫司可抑制iNOS的表达,从而减轻移植肾组织的急性排斥反应。

Expression of inductive nitricoxide synthase in the transplanted renal tissue and the effects of Aminoguanidine / Tacrolimus on acute allograft rejection following renal transplantation

Objective: To observe the expression of iNOS in the transplanted renal tissue and the effect of Aminoguanidine(AG)/ Tacrolimus on acute allograft rejection following renal transplantation.Methods: Rat models of renal orthotopic transplantation were divided into an isograft group(n=5,SD to SD rats) and an allograft group,the latter including 3 subgroups(SD to Wistar rats): acute rejection(n=5),AG treatment(n=5) and Tacrolimus treatment(n=5).The grafts harvested on day 7 were subjected to histopathological examination,RT-PCR analysis of the iNOS mRNA expression and immunohistochemical measurement of the iNOS activity.The effects of AG /Tacrolimus on the acute allograft rejection following renal transplantation were studied.Results: iNOS expressed strongly in the acute allograft rejection group,with statistically significant differences from the AG,Tacrolimus and isograft groups(P<0.01).Conclusion: During acute allograft rejection in rat renal orthotopic transplantation,the expression of iNOS increased markedly and the increase was closely related to the severity of acute allograft rejection.AG and Tacrolimus could inhibit the expression of iNOS and attenuate acute allograft rejection in the transplanted renal tissue.