大鼠原位肝移植急性排斥模型的建立及论证

摘要

目的 建立大鼠原位肝移植急性排斥模型.方法 通过改良的二袖套法,以Lewis (RTl1)大鼠作为供体,Brown Norway(BN Rtln)大鼠作为受体,进行原位肝移植.实验组(n=15),术后未进行特殊的干预；对照组(n=15),术后1-7 d用FK506 0.2 mg·kg-1·d-1灌胃.术后观察两组受体的生存情况,检测肝功能、细胞因子变化、肝组织急性排斥反应和肝细胞凋亡.结果 实验组平均生存时间(9.17±1.17)d,明显短于对照组的(50.17±8.50) d(P＜0.05);术后实验组在肝功能各指标水平、细胞因子(IL-2,IFN-γ)表达水平、肝组织排斥活动指数(RAI)和肝细胞凋亡数方面明显高于对照组,而实验组的细胞因子(IL-4,IL-10)浓度明显低于对照组(P＜0.05或P＜0.01).结论 以近交系Lewis大鼠为供体、BN大鼠为受体进行肝移植,发生的急性排斥反应强烈而且稳定,是较为理想的大鼠肝脏移植急性排斥模型.%Objective To establish an acute rejection rat model of orthotopic liver transplantatioa Methods With a modified two-cuffed technique, orthotopic liver transplantation was performed in Lewis(RTl1) to Brown Norway(BN,Rtl) rats. The rats in experimental group(n=15) were not specially treated, while the rats in control group(n=15) were given FK506 0.2 mg · kg-1 · d-1 by gastric gavage during 1-7 days after operation. Postoperative living status of rats was observed and postoperative hepatic function, cytokine, hepatic acute rejection and liver cell apoptosis were detected and compared between two groups. Results The rats in experimental group survived averagely (9.17±1.17) days, which was shorter than (50. 17 ± 8. 50) days in control group (P<0. 05). All indicators of liver function,expression levels of IFN-7 and IL-2,RAI in hepatic tissues and the apoptosis number of liver cells of rats after operation were obviously higher, but IL-4 and IL-10 were lower, in experimental group than those in control group (P<0. 05 or P<0. 01). Conclusion The acute rejection rat model of orthotopic liver transplantation established between inbred line rats with Lewis rats as donors and BN rats as receptors is an ideal acute rejection model with strong and stable rejection.