大鼠原位肝臟移植模型的建立和改良以及不同品系組合的大鼠肝移植排斥反應(yīng)的比較
發(fā)布時間:2018-04-17 00:25
本文選題:肝臟移植模型 + 急性排斥反應(yīng); 參考:《廈門大學》2009年碩士論文
【摘要】: 背景和目的構(gòu)建一個穩(wěn)定而具有典型移植排斥反應(yīng)的動物模型是肝臟移植研究的基礎(chǔ)。大鼠原位肝臟移植模型是最常用的模型之一。本實驗研究的目的就是建立改良的大鼠原位肝臟移植模型,并通過對不同品系大鼠肝臟移植模型的比較,探索理想的急性排斥模型,同時檢測T細胞亞群在急性排斥反應(yīng)中的表達。 研究方法采用Kamada“雙袖套法”建立大鼠原位肝臟移植模型,對術(shù)中供肝的分離、切取、灌注、植入以及術(shù)后的護理觀察等方面進行改良;以大鼠SD(供體)→SD(受體)為對照組,建立Wistar→SD、Lewis→BN、DA→Lewis三種不同品系組合的大鼠肝臟原位移植排斥模型,在術(shù)后恢復情況、生存時間、肝功能、組織病理學等方面進行比較,探索最理想的急性排斥模型;流式檢測T細胞亞群(CD3~+、CD3~+CD4~+、CD3~+CD8~+、CD4~+CD25~+、NKT)在急性排斥反應(yīng)中的表達。 研究結(jié)果建立了改良的大鼠原位肝臟移植模型,手術(shù)簡單易行,穩(wěn)定可靠,可重復性高,大鼠術(shù)后恢復好;大鼠SD→SD屬于同源耐受組合,Wistar→SD屬于輕度或不明確性排斥反應(yīng)組合,雖然Lewis→BN、DA→Lewis組合都發(fā)生了明顯的急性排斥反應(yīng),但DA→Lewis組合是最理想的急性排斥反應(yīng)模型;與耐受組比較,急性排斥反應(yīng)受體外周血CD3~+及CD3~+CD4~+表達較多,CD3~+CD4~+/CD3~+CD8~+比值較高,脾臟和淋巴結(jié)中NKT細胞表達較多,而CD4~+CD25~+的表達無統(tǒng)計學差異。 研究結(jié)論改良后的大鼠原位肝臟移植模型簡單易行、穩(wěn)定可靠;大鼠DA→Lewis組合是理想的急性排斥模型;大鼠急性排斥反應(yīng)的發(fā)生可能與受體效應(yīng)性T細胞亞群CD4/CD8比例的上調(diào)以及NKI調(diào)節(jié)性T細胞亞群的下調(diào)有關(guān)。本研究為進一步研究大鼠移植排斥反應(yīng)的機制和移植免疫耐受的誘導打下了一定的基礎(chǔ)。
[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.
【學位授予單位】:廈門大學
【學位級別】:碩士
【學位授予年份】:2009
【分類號】:R657.3;R-332
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2 邵慧,孫德明;免疫調(diào)節(jié)細胞的研究現(xiàn)況:NKT細胞[J];上海免疫學雜志;2003年03期
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