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小剂量FK506作用下同种脾组织移植诱导大鼠原位肝移植术后免疫耐受的机制
史永照,李先兴,施晓敏,丁国善,傅志仁
0
(第二军医大学长征医院器官移植研究所,上海,200003)
摘要:
目的:观察小剂量FK506作用下同种脾组织移植对大鼠肝移植术后免疫耐受的影响,探讨其可能的机制.方法:实验分5组(每组大鼠8只),同种肝移植组(A组)以纯系雄性Lewis大鼠为供体、雌性BN大鼠为受体进行同种原位肝移植;同种肝移植+小剂量FK506治疗组(B组)于肝移植术后口服途径给予小剂量FK506(0.25 mg/kg);同种肝脾联合移植组(C组)于肝移植同时移植供体脾脏;同种肝脾联合移植+小剂量FK506治疗组(D组)于肝脾联合移植后口服途径给予小剂量FK506;异体脾组织移植组(E组)于同种原位肝移植同时移植第三品系大鼠脾脏组织,术后进行小剂量FK506治疗.观察各组的存活期,并分析受体脾脏T淋巴细胞对同种抗原的反应性、嵌合体的形成情况以及肝脏病理变化.结果:与其他各组相比,C组大鼠的存活期明显延长;其受体T细胞同种抗原反应性明显降低;受体脾脏中供体阳性细胞明显升高(P<0.01),且在60 d后受体脾脏中供体阳性细胞仍然较高;肝脏病理分析也未见明显排斥反应.结论:小剂量FK506作用下同种脾脏移植能明显诱导受体大鼠原位肝移植术后嵌合体的形成,降低受体T细胞对同种抗原的反应性,促进免疫耐受.
关键词:  脾、嵌合体、免疫耐受、肝移植
DOI:10.3724/SP.J.1008.2006.00946
投稿时间:2006-04-10修订日期:2006-08-28
基金项目:国家自然科学基金(30471643).
Allogeneic spleen tissue transplantation combined with low-dose FK506 in induction of allograft tolerance in orthotopic liver transplant rats
SHI Yong-zhao,LI Xian-xing,SHI Xiao-min,DING Guo-shan,FU Zhi-ren
(第二军医大学长征医院器官移植研究所,上海,200003)
Abstract:
Objective. To investigate the influence of allogeneic spleen tissue transplantation with low-dose FKS06 on allograft tolerance in rats receiving orthotopic liver transplant and the related mechanism. Methods: Female Brown Norway (BN) rats were divided into 5 groups (eight rats in each group). Rats in Group 1 received orthotopic allogeneic liver transplantation using inbred Lewis rats as donors. Rats in Group 2 received Lewis liver transplantation+ low-dose FK-506 (0.25 mg/kg FK-506 was orally given after transplantation). Rats in Group 3 received Lewis liver transplantation+ Lewis spleen transplantation. Rats in Group 4 received Lewis liver transplantation+ Lewis spleen transplantation+ low-dose FK-506. Rats in Group 5 received Lewis liver+SD spleen transplantation+low-dose FK-506. The survival periods were recorded for each group. The forming of chimerism, the responsiveness of T cells to alloantigen and the pathological changes of transplanted liver were analyzed after treatment. Results: Compared with rats in other groups, rats in Group 4 had an obviously longer survival time, an obviously reduced T cell responsiveness to alloantigen, and obviously increased donoro-positive cells (remained for 60 days after transplantation) (P〈0.05). There was no significant pathological evidence of rejection. Conclusion: Allogeneic spleen transplantation combined with low-dose FKS06 treatment can induce graft immune tolerance in orthotopic allogeneic liver transplant recipients through promoting the formation of chimerism and T cells hyporesonsiveness to alloantigen
Key words:  spleen  chimerism  immune tolerance  liver transplantation