预输注5fu处理的同种异基因淋巴细胞诱导大鼠肝移植免疫耐受的初步研究-preliminary study on immune tolerance induced by allogeneic lymphocytes pretreated with 5 fu in rat liver transplantation.docxVIP

广州医学院硕士研究生学位论文 广州医学院硕士研究生学位论文 PAGE PAGE 4 2. 病理情况：C 组大鼠肝脏病理改变呈急性轻度排斥反应，肝细胞条索状排列基本 整齐，肝小叶结构存在；中央静脉血管少量炎性细胞侵润；汇管区少量淋巴细胞侵 润。A 组呈急性重度排斥反应；B、D 组呈急性中度排斥反应。C 组优于 A、B、D 组。 3. 免疫组化 CD4、CD8 表达：肝小叶中，A 组 CD8+T 细胞的总累积光密度值(IOD SUM)高于 B 组、C 组和 D 组(P0.05)。B 组、C 组和 D 组无差异(P0.05)。汇管区， A 组 CD8+T 细胞的 IOD SUM 高于 B 组、C 组和 D 组(P0.05)。C 组低于 B 组和 D 组(P0.05)。B 组和 D 组无差异(P0.05)。CD4 在肝小叶和汇管区均无表达。 4. 免疫组化 FasL 表达：肝小叶中，C 组 FasL 细胞的 IOD SUM 高于 A 组、B 组和 D 组(P0.05)。B 与 D 组无显著性差异(P0.05)。A 组低于 B、C、D 组(P0.05)。 汇管区，A 组 FasL 细胞的 IOD SUM 低于 B、C、D 组(P0.05)。C 组高于 A、B、 D 组(P0.05)。B 与 D 组无显著性差异(P0.05)。 结论 1. 成功建立了 Wistar-SD 大鼠原位肝移植模型。 2. 大鼠肝移植急性排斥中，CD8+T 细胞是主要参与者，CD4+T 细胞为辅助者。 3. 预输注低浓度 5-Fu 处理的同种异基因淋巴细胞可以诱导移植肝 FasL 表达上调。 4. 耐受机制可能是通过 Fas/FasL 通路，诱导肝小叶及汇管区的 CD8+T 细胞凋亡来 实现。 关键词：肝移植；供体淋巴细胞输注；排斥反应；免疫耐受 Study on immune tolerance induction in rat liver transplantation by pre-infusion of 5-Fu treated allogeneic lymphocytes ABSTRACT Objective To investigate the mechanism of immune tolerance induction in rat liver transplantation by pre-infusion of allogeneic lymphocytes treated with 5-Fu. Methods Wistar and SD rats were used as liver transplantation donors and recipients, respectively. And the model of rat orthotopic liver transplantation was established with two-cuff-technique. Wistar allogeneic lymphocytes were cultured in different concentrations in vitro. Animal were divided randomly into 4 groups as follows: Group A(n=10), take as control liver transplanted from Wistar to SD without any treatment; Group B(n=10), recipients were infused lymphocytes(5×106) from Wistar rat 7 days and 4 days separately before transplantation; Group C(n=10), recipients were infused 5-Fu(7.5ug/ml) treated allogeneic lymphocytes(5×106) from Wistar rat 7 days and 4 days separately before transplantation; Group D(n=10), recipients were infused 5-Fu(15ug/ml) treated allogeneic lymphocytes(5×106) from Wistar rat 7 days and 4 days separately before transplantation; Observations on post transplant clinical course. 7 days