不使用免疫抑制剂大鼠胚胎后肾同种移植器官形成

Organogenesis of developing metanephroi allografted into nonimmunosuppressed adult rats

目的:探索扩大器官移植供源,诱导免疫耐受的新途径.方法:在不使用免疫抑制剂的情况下,将远交系SD大鼠孕第14～19天(E14～E19)的胚胎后肾分组移植到行单侧肾脏切除的成年SD大鼠的腹腔,移植后4周开腹观察器官形成情况,并取标本进行生化和组织病理学检查.结果:植入大网膜28 d后,E18、E19胚胎后肾增大,但已被纤维结缔组织完全替代;E16、E17胚胎后肾移植后出现排斥反应,使用环孢霉素A者,E17胚胎后肾则发育良好;E14、E15胚胎后肾植入大网膜或残留肾蒂周围,发育的肾单位、集合管、输尿管结构正常,组织中少有淋巴细胞浸润;移植时宿主肾脏不切除而植入胚胎后肾,其后肾不发育;部分E15、E16胚胎后肾出现输尿管或肾盂积液现象,积液中尿素氮、肌酐值浓度与尿液中接近.结论:不使用免疫抑制剂的E14、E15组或使用环孢霉素A的E17组移植后肾在同种成年大鼠体内能够再血管化,并形成器官,显示其具有一定的泌尿功能.多种因素影响胚胎后肾的移植效果,但是排斥反应仍然是最主要的制约.

Objective： To explore novel methods of possible donor organ supply and immunologic tolerance induction of organ transplantation. Methods： Whole metanephroi from d14-19 （E14-E19） embryos of pregnant rats were grouped and allografted into the omenta or near remnants of renal vessels of nonimmunosupressed adult rats. At the time of implantation ,host rats underwent unilateral nephrectomy. Four weeks after implantation ,allografted metanephroi in host rats were removed for gross,biochemical and histopathological examination. Results： Four weeks post-implantation,（1） E19 and E18 metanephroi had enlarged,but were replaced by connective tissues. （2） E17 and E16 metanephroi showed the signs of acute rejection such as hypercellular glomeruli and lymphocyte infiltration in peritubular spaces. E16 grafted metanephroi underwent mild acute rejection of Banff schema,while E17 had moderate or severe acute rejection. When Cyclosporine A was administrated,E17 metanephroi formed mature nephrons and collecting ducts with few lymphocyte infiltration. （3） Metanephroi from E15 and E14 embryos allografted into the omentum or near remnants of renal vessels of uninephrectomized adult rats were enlarged and vascularized,and formed mature tubules and glomeruli. （4） The concentrations of urea nitrogen and creatinine in cyst fluid of E15 and E16 metanephroi were increased 40-fold and 50-fold,which were comparable to those in bladder urine. （5） In contrast,rat metanephroi did not grow or differentiate in rats without host kidney resection. Conclusion： E14 and E15 metanephroi allografted into nonimmunosuppressed adult rats or E17 into cyclosporine-treated hosts undergo growth and differentiation and become vascularized. A variety of factors affect the growth and development of allografted metanephroi,while rejection is the main one.