霉酚酸对树突状细胞延长移植肾存活效应的影响.DOCVIP

临床医学论文-霉酚酸对树突状细胞延长移植肾存活效应的影响 ????????? 作者：李杰，张银甫，黄赤兵，范明齐，王平贤，冯嘉瑜，肖亚 [摘要］? 目的? 探讨霉酚酸(mycophenolic acid,MPA)对树突状细胞（dendritic cells,DC）延长移植肾存活效应的影响。方法? 以BN、Lewis大鼠为肾移植供、受体；在供体DC培养过程中加入两种浓度MPA，以CTLA-4Ig基因转染DC使之成为表达CTLA-4Ig的致耐受DC；观察DC形态变化并检测受体脾细胞对上述DC的刺激反应。将未处理的致耐受DC以及0.05 μmol/L MPA处理DC于肾移植前72 h分别注入受体(组1、组2)，注入供体DC的受体为组3，未注入DC的受体为对照(组4)，观察受体血肌酐变化和移植肾存活时间。结果? MPA组DC形态老化延缓，脾细胞对两种浓度MPA处理的DC刺激反应均显著低于对未经MPA处理致耐受DC的刺激反应；与对照相比，组1、组2移植肾存活时间显著延长（P0.01），其中组2延长更为明显［（76.1±14.6）天vs（8.9±0.8）天，P0.001］，组3存活时间显著缩短（5.3±0.6天,P0.05）。术后45天后组2血肌酐水平明显低于组1。结论? MPA预处理可降低致耐受DC的抗原提呈能力，提高其延长移植肾存活的效能。 　　［关键词］? 霉酚酸；树突状细胞；肾移植 ??? Influence of mycophenolic acid on survival prolongation of renal allografts with tolerogenic dendritic cells ??? ［Abstract］? Objective? To study the influence of mycophenolic acid (MPA) on survival prolongation of renal allografts with tolerogenic dendritic cells(DC)in rats.Methods? The influence of MPA on CTLA-4Ig-gene-transferred donor DCs was observed in vitro morphologically and functionally. The influence of MPA on the survival time and function of the renal allografts was observed in a BN→Lewis kidney transplantation model with recipients treated by CTLA-4Ig-gene-transferred donor DCs.Results? The maturation and aging of DC were delayed and the stimulating ability of DC to recipient splenic cells was impaired significantly with the adding of MPA. Survival time of renal allografts in CTLA-4Ig-gene-transferred DC group was prolonged significantly (compared with control,57.1±13.4 d vs 8.9±0.8 d,P0.01) and further prolonged with the adding of MPA (76.1±14.6 d vs 8.9±0.8 d，P0.001).The allografts functioned well even after forty-five days postoperatively in recipient treated with MPA preconditioned DC.Conclusion? MPA preconditioning impairs the ability of?? antigen presentation of CTLA-4Ig-gene-transferred donor DCs and enhances it’s efficacy of? survival prolongation of renal allografts in rats. ??? ［Key words］? mycophenolic acid;dendritic cells;kidney transplantation ??? 树