FTY720介导淋巴细胞凋亡抑制小肠移植的移植物抗宿主免疫反应

FTY720-induced lymphocyte apoptosis inhibits acute graft versus host disease in rat small bowel transplantation

目的 探讨免疫调节药物FTY720对小肠移植后急性移植物抗宿主病（GVHD）的治疗效果及其作用机制.方法 应用Wistar-Furth（WF）大鼠作为供体,WF和ACI大鼠的子代（F1）作为受体,同种异基因异位全小肠移植的技术方法建立GVHD的动物模型.移植受体分为实验组和对照组,每组6只.实验组从移植手术当日开始予以FTY720治疗,持续14 d;对照组在相同的时间段口服蒸馏水.术后第15天,提取受体靶器官肝脏、小肠及移植物小肠的淋巴细胞,应用免疫组织化学（免疫组化）TUNEL法和流式细胞仪检测两组淋巴细胞凋亡的变化.结果 对照组大鼠术后均死亡于GVHD,平均生存时间（16.0±1.7）d,实验组大鼠均长期成活超过100 d,两组差异具有统计学意义（P＜0.01）.免疫组化TUNEL法检测结果显示,实验组肝脏和移植物小肠黏膜的淋巴细胞凋亡比率均明显高于对照组,差异具有统计学意义（P＜0.05）.流式细胞技术分析结果显示,实验组大鼠移植物小肠黏膜内凋亡的淋巴细胞百分比为19.4%,明显高于对照组的11.8%（P＜0.05）;而肝脏凋亡的淋巴细胞百分比两组差异无统计学意义（P＞0.05）.结论 FTY720可能通过诱导淋巴细胞的凋亡,减少和抑制GVHD对靶器官的损害,改善移植大鼠的预后.

Objective To investigate the effect and mechanism of FTY720 on acute graft versus host disease （GVHD） in rat small bowel transplantation （SBTx）.Methods Heterotopic SBTx was performed using a parent （WF）-into-F1 （WFxACI）rat combination.Recipient rats were divided into experimental group （n=6） and control group（n=6）.Rats in the experimental group were administered with FTY720 at 0.5 mg/kg for 14 days.Lymphocyte apoptosis in the liver and the mucosa of intestine and graft was detected by TUNEL and flow cytometry 15 days after transplantation.Recipient survival and lymphocyte apoptosis were compared between the two groups.Results Recipients in the control group died of GVHD after a mean survival time of （16±2.1） days.FTY720-treated recipients had a significantly longer survival （〉100 days）.After administration of FTY720,the percentage of apoptotic lympbocytes was significantly increased in the graft as compared to that in the control group by flow cytometry.The ratio of apoptotic lymphocyte in the liver and graft was also significantly higher in the experimental group by TUNEL.Conclusion FTY720 effectively induces the lymphocyte apoptosis,inhibits the lesion of target tissues by GVHD,and prolongs the recipient survival.