大鼠原位肝脏移植模型的建立和改良以及不同品系组合的大鼠肝移植排斥反应的比较

发布时间：2018-04-17 00:25

本文选题：肝脏移植模型 + 急性排斥反应　；参考：《厦门大学》2009年硕士论文

【摘要】： 背景和目的构建一个稳定而具有典型移植排斥反应的动物模型是肝脏移植研究的基础。大鼠原位肝脏移植模型是最常用的模型之一。本实验研究的目的就是建立改良的大鼠原位肝脏移植模型,并通过对不同品系大鼠肝脏移植模型的比较,探索理想的急性排斥模型,同时检测T细胞亚群在急性排斥反应中的表达。研究方法采用Kamada“双袖套法”建立大鼠原位肝脏移植模型,对术中供肝的分离、切取、灌注、植入以及术后的护理观察等方面进行改良;以大鼠SD(供体)→SD(受体)为对照组,建立Wistar→SD、Lewis→BN、DA→Lewis三种不同品系组合的大鼠肝脏原位移植排斥模型,在术后恢复情况、生存时间、肝功能、组织病理学等方面进行比较,探索最理想的急性排斥模型;流式检测T细胞亚群(CD3~+、CD3~+CD4~+、CD3~+CD8~+、CD4~+CD25~+、NKT)在急性排斥反应中的表达。研究结果建立了改良的大鼠原位肝脏移植模型,手术简单易行,稳定可靠,可重复性高,大鼠术后恢复好;大鼠SD→SD属于同源耐受组合,Wistar→SD属于轻度或不明确性排斥反应组合,虽然Lewis→BN、DA→Lewis组合都发生了明显的急性排斥反应,但DA→Lewis组合是最理想的急性排斥反应模型;与耐受组比较,急性排斥反应受体外周血CD3~+及CD3~+CD4~+表达较多,CD3~+CD4~+/CD3~+CD8~+比值较高,脾脏和淋巴结中NKT细胞表达较多,而CD4~+CD25~+的表达无统计学差异。研究结论改良后的大鼠原位肝脏移植模型简单易行、稳定可靠;大鼠DA→Lewis组合是理想的急性排斥模型;大鼠急性排斥反应的发生可能与受体效应性T细胞亚群CD4/CD8比例的上调以及NKI调节性T细胞亚群的下调有关。本研究为进一步研究大鼠移植排斥反应的机制和移植免疫耐受的诱导打下了一定的基础。
[Abstract]:Background and objective to construct a stable animal model with typical graft rejection is the basis of liver transplantation.The rat orthotopic liver transplantation model is one of the most commonly used models.The purpose of this study was to establish an improved orthotopic liver transplantation model in rats, and to explore an ideal model of acute rejection by comparing the liver transplantation models of different strains of rats.The expression of T cell subsets in acute rejection was also detected.Methods the rat orthotopic liver transplantation model was established by using Kamada "double cuff method" to improve the separation, extraction, perfusion, implantation and postoperative nursing observation of the donor liver, and the SD receptor was used as the control group.The orthotopic transplantation rejection model of rat liver was established with three different combinations of Wistar. The survival time, liver function and histopathology were compared in order to explore the most ideal acute rejection model.The expression of CD3 ~ CD3 ~ CD4 ~ + CD3 ~ 8 ~ + CD4 ~ 25 ~ nkT in T cell subsets was detected by flow cytometry in acute rejection.Results the modified orthotopic liver transplantation model was established in rats. The operation was simple, reliable, stable and reproducible, and the rats recovered well after operation.SD belongs to the homologous tolerance group. SD belongs to mild or uncertain rejection combination. Although the combination of Lewis BNDA and Lewis has obvious acute rejection, DA Lewis combination is the most ideal acute rejection model.Compared with the tolerance group, the expression of CD3 ~ and CD3- CD4 ~ ~ in peripheral blood of acute rejection receptor was higher than that in the control group. The expression of NKT cells in spleen and lymph nodes was higher than that in the control group, but there was no significant difference in the expression of CD4 ~ ~ CD25 ~ ~ in peripheral blood.Conclusion the modified rat orthotopic liver transplantation model is simple, stable and reliable, and DA Lewis combination is an ideal model for acute rejection.The occurrence of acute rejection in rats may be related to the up-regulation of receptor effector T cell subsets (CD4/CD8) and the down-regulation of NKI regulatory T cell subsets.This study laid a foundation for further study on the mechanism of allograft rejection and the induction of transplantation immune tolerance in rats.
【学位授予单位】：厦门大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R657.3;R-332

【参考文献】