不同胎龄大鼠移植后肾细胞排斥反应与发育的关系

Jian Xu, Yahui Sun, Chunyue Xu, Yening Huang, Liang-jie Hong, F. Zeng
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摘要

目的探讨细胞排斥反应与不同胎龄同种异种移植原基发育的关系。方法将胚胎期E14~E19的大鼠后肾移植至远交种网膜内(SD→SD, 6组,每组≥10只;E15-E17SDCsA, 3组,各n=15)、同基因(Lewis→Lewis, 5组,各n=8)、异基因(Lewis→BN, E15BN n=6各E15BNCsA n=10各E16BNCsA n=10各)大鼠和异种(Lewis→c57组,E15C57 n=10各,E15C57CsA, n=8各;Lewis→Balb/c裸鼠,3组,每组n=10)。采用组织病理学、Banff分级法和电子显微镜(EM)对移植物发育进行评估。同样,测定生化指标和肌酐清除率。结果移植后4周,SD→SD组E14-E17SD后肾出现Banff排斥反应。E14/E15SD显著轻于E16/E17SD (p0.05)。E14Lewis和E18Lewis组大鼠后肾分化明显低于E16 Lewis组。Lewis→C57BL/6中,E15后肾在移植后第14天发生排斥反应(n=10),给予CsA (15 mg·kg-1·d-1, n=8)后无明显改善。Lewis→Balb/c裸鼠E15~E17Balb/c后肾发育良好。光镜和电镜检查显示肾单位和收集管正常,积液湿重、肌酐、尿素氮无明显差异(P < 0.05)。E15Lewis和E16Lewis的湿重和肌酐清除率与E15SDCsA和E16SDCsA有显著差异。E15SDCsA湿重最大,肌酐清除率最低(P<0.01)。结论E15、E16和E17大鼠后肾在同种异体和异种异体移植过程中排异反应得到控制后,其发育特征相似。细胞免疫原性因素仍然是其发展的主要障碍。关键词:后肾胚;免疫排斥反应;免疫抑制剂;器官发生
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Relationship between cellular rejection and development of rat transplanted metanephroi from different gestational ages
Objective To explore the relationship between cellular rejection and the development of allo-or xenografted primordia from different gestational ages. Methods Whole rat metanephroi from embryonic day E14~E19 were transplanted into omenta of outbred (SD→SD, 6 groups, n≥10 each; E15-E17SDCsA, 3 groups, n=15 each), syngeneic (Lewis→Lewis, 5 groups, n=8 each), allogeneic (Lewis→BN, E15BN n=6 each E15BNCsA n=10 each, E16BNCsA n=10 each) rats and xenogeneic (Lewis→C57groups, E15C57 n=10 each, E15C57CsA, n=8 each; Lewis→Balb/c nude mice, 3 groups, n=10 each) recipients. Histopathology, Banff’s grading and electron microscopy (EM) were utilized for assessing the graft development. Similarly, biochemical indicators and creatinine clearances were measured. Results At 4 weeks post-transplantation, in SD→SD groups, E14-E17SD metanephroi developed with Banff’s rejections. E14/E15SD was significantly lighter than E16/E17SD (P 0.05). E14Lewis and E18Lewis rats had significantly poorly differentiated metanephroi than those in E16 Lewis group. In Lewis→C57BL/6, E15 metanephroi were rejected at Day 14 post-transplantation (n=10) and no improvement was evident after CsA dosing (15 mg·kg-1·d-1, n=8). In Lewis→Balb/c nude mice, all E15~E17Balb/c metanephroi developed well. Both light microscopy and EM examination showed normal nephrons and collecting ducts and wet weight, creatinine or urea nitrogen of effusion showed no significant difference (P>0.05). E15Lewis and E16Lewis had significantly different values of wet weight and creatinine clearances from those of E15SDCsA and E16SDCsA. E15SDCsA had the greatest wet weight and the lowest creatinine clearance rate (P<0.01). Conclusions After controlling rejection during allo-and xenotransplantations, E15, E16 and E17 rat metanephros have similar development characteristics. And cellular immunogenic factors still remain the major barriers to their developments. Key words: metanephrogenic blastema; immunological rejection; immunosuppressant; organogenesis
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