序贯疗法改善大鼠小肠移植慢性排斥反应的实验研究

首都医科大学学报 ›› 2010, Vol. 31 ›› Issue (2): 201-205.

序贯疗法改善大鼠小肠移植慢性排斥反应的实验研究

李小松^*, 朱伟伟, 邱晓虹, 张金哲

首都医科大学附属北京儿童医院外科

收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2010-04-21 发布日期:2010-04-21
通讯作者: 李小松

Sequential Treatment Ameliorates Chronic Rejection in Rat after Orthotopic Small Bowel Transplantation

LI Xiao-song^*, ZHU Wei-wei, QIU Xiao-hong, ZHANG Jin-zhe

Department of Surgery, Beijing Children's Hospital, Capital Medical University

Received:1900-01-01 Revised:1900-01-01 Online:2010-04-21 Published:2010-04-21
Contact: LI Xiao-song

摘要/Abstract

摘要： 目的本研究旨在通过序贯疗法治疗大鼠小肠移植慢性排斥反应的实验研究，探索小肠移植慢性排斥反应的病理特点及其免疫耐受机制。方法本研究应用大鼠原位小肠移植为模型。FK506 加雷帕霉素序贯疗法控制慢性排斥反应。HE，Masson和Elastin染色用于反映移植物的组织病理学变化，免疫组化和流式细胞方法检测移植物及血液中细胞浸润和抗移植物循环抗体的表达。结果非序贯治疗组大鼠只有21%长期存活，而序贯治疗组大鼠91.7%得到长期存活。序贯治疗组大鼠表现出较完整的肠道及肠系膜组织学形态，并只有轻微的血管闭塞和胶原纤维的沉积。同时移植肠管肠系膜iNOS阳性吞噬细胞浸润显著增多，而抗移植物循环抗体显著降低。结论序贯疗法可明显缓解大鼠小肠移植慢性排斥反应发生，其机制可能与iNOS阳性吞噬细胞浸润和抗移植物循环抗体降低有关。

关键词: 小肠移植, 慢性排斥反应, 病理学, 免疫耐受

Abstract: Objective This study aimed to evaluate the effect of a sequential treatment on small bowel transplantation(SBT) allograft survival and attempted to elucidate the underlying mechanisms to prevent chronic rejection(CR). Methods Sequential treatment with rapamycin (Rapa) following a FK506 pretreatment was administered to control CR in rat orthotopic SBT model. The recipients were sacrificed for evaluation of CR by morphological and immunohistochemical analysis. The production of antidonor isotype specific antibody was quantified by flow cytometry. Results In control group, 79% recipients developed severe vasculopathy and parenchymal fibrosis and died of CR around 90 postoperative day. With sequential treatment, 91.7% recipients survived, showed reduced severity of vasculopathy, markedly reduced fibrosis in the mesentery, and inhibition of the production of the Th1 and Th2 associated isotype specific antibodies. Conclusion The sequential treatment was effective in the control of CR and dramatically prolonged rat allograft survival, and may contribute in a clinical setting towards better outcomes in SBT.

Key words: small bowel transplantation, chronic rejection, pathology, immunological tolerance

中图分类号:

R 656.7

李小松;朱伟伟;邱晓虹;张金哲. 序贯疗法改善大鼠小肠移植慢性排斥反应的实验研究[J]. 首都医科大学学报, 2010, 31(2): 201-205.

LI Xiao-song;ZHU Wei-wei;QIU Xiao-hong;ZHANG Jin-zhe. Sequential Treatment Ameliorates Chronic Rejection in Rat after Orthotopic Small Bowel Transplantation[J]. Journal of Capital Medical University, 2010, 31(2): 201-205.

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