大鼠近交系间原位肝移植急性排斥模型的建立与评价

背景：目前国内常用的封闭群品系大鼠(SD与Wistar大鼠)所建立肝移植急性排斥模型并不理想，易产生肝移植耐受。目的：通过二袖套法建立稳定的DA-Lewis大鼠原位肝移植急性排斥模型。方法：实验分为两组：同基因组：Lewis-Lewis 24例；异基因组：DA-Lewis 24例。观察移植后一般情况及移植后存活时间，两组受体分别于移植后3，5，7，10 d随机取3只处死取标本，观察肝脏组织病理变化，测定天冬氨酸转氨酶、总胆红素、细胞因子水平变化。结果与结论：同基因组大鼠无急性排斥反应表现，中位生存时间超过100 d，肝脏组织发生轻度形态学改变。异基因组大鼠移植后黄疸明显，中位生存时间为11 d，移植后第7天肝脏组织病理表现典型急性排斥反应(Banff国际标准)。同期相比异基因组天冬氨酸转氨酶、总胆红素、细胞因子水平均高于同基因组(P < 0.001)。提示，DA-Lewis是稳定的大鼠肝移植急性排斥模型，是研究肝移植排斥反应及免疫耐受的理想动物模型。

Establishment and evaluation of an acute rejection model of orthotopic liver transplantation in inbred rats

BACKGROUND: The models commonly used from closed population at present were not well ideal, which easy lead to liver transplantation tolerance. OBJECTIVE: To establish a stable rat model of acute rejection following allograft liver transplantation from DA to Lewis by two-cuff method.METHODS: The rats were allocated to the isogene group (n=24, liver grafts from Lewis rat to Lewis rat) or allogene group (n=24, liver grafts from DA rat to Lewis rat). The general states and survival duration of the rats after transplantation were observed. Three recipient rats in each group were randomly executed at 3, 5, 7 and 10 days for observation of histopathological changes in the liver tissues and detection of serum levels of aspartate aminotransferase (AST), total bilirubin, and cytokine.RESULTS AND CONCLUSION: In the isogene group,a mild morphological change in the liver tissue was found but no acute rejection occurred, which the median survival duration was more than 100 days. In the allogene group, however, obvious jaundice developed postoperatively, which the median survival duration was 11 days, and a typical acute rejection occurred pathologically in the liver tissue at 7 days according to the Banff standards. Levels of AST, total bilirubin, and cytokine were respectively significantly higher in allogene group than that in isogene group at 3, 5, 7 and 10 days (P < 0.001). The acute rejection of DA to Lewis orthotopic liver transplantation model is stable; it can be effectively used to study allograft rejection and tolerance.