Flt3L联合亚剂量雷帕霉素延长小鼠心脏移植物存活的机制研究

发布时间：2018-07-03 19:44

本文选题：Flt3配体 + 雷帕霉素　；参考：《华中科技大学》2012年博士论文

【摘要】：背景：诱导同种异体抗原特异性无应答是干预移植排斥反应的最佳策略。本课题通过联合给予Flt3L和亚剂量雷帕霉素，研究其在小鼠同种异体心脏移植中的作用，并探讨该作用的细胞和分子机制。方法：受者C57BL/6小鼠尾静脉注射Flt3L（10μg/天），持续给药10天后进行腹腔异位心脏移植，供者为BALB/c小鼠。术后0天起给予受者小鼠亚剂量雷帕霉素（2mg/kg）灌胃处理。观察小鼠移植物存活时间，流式细胞术检测T细胞和DC表型，，混合淋巴细胞培养检测T细胞功能状态，Westernblot和免疫组化检测组织细胞自噬相关蛋白Beclin-1和LC3表达。结果：与对照组相比，Flt3L联合亚剂量雷帕霉素可显著减缓小鼠心脏移植排斥反应并延长移植物存活时间。移植物存活时间延长与调节性DC、调节性T细胞（Treg）和抑制性细胞因子IL-10水平相关。另外发现，移植物细胞自噬增强也是是导致移植物存活延长的重要因素。结论：Flt3L联合雷帕霉素可作为诱导移植耐受的有效干预策略。
[Abstract]:Background: induction of allogeneic antigen-specific nonresponse is the best strategy for intervention of allograft rejection. In this study, the effects of Flt3L and rapamycin on allogeneic heart transplantation in mice were studied, and the cellular and molecular mechanisms of the action were discussed. Methods: C57BL / 6 mice were injected with Flt 3L (10 渭 g / d) by tail vein for 10 days. The recipient mice were given sub-dose rapamycin (2mg/kg) intragastrically at 0 days after operation. The survival time of mouse grafts was observed, the phenotypes of T cells and DC were detected by flow cytometry, the functional status of T cells was detected by Western blot and the expression of autophagy associated proteins Beclin-1 and LC3 was detected by immunohistochemistry. Results: compared with the control group, Flt3L combined with rapamycin could significantly reduce the rejection of heart transplantation and prolong the survival time of the graft. The prolongation of graft survival time was associated with the levels of regulatory DCG, regulatory T cells (Treg) and inhibitory cytokine IL-10. In addition, the enhancement of graft cell autophagy was also found to be an important factor in prolonging graft survival. Conclusion the combination of Flt3 L and rapamycin can be used as an effective intervention strategy to induce graft tolerance.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R392

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