大鼠胚胎胸腺和后肾原基联合异种移植与诱导免疫耐受的初步研究  

Preliminary study on tolerance induction by combined xenotransplantation of rat thymus and meta- nephros anlagen

作　　者：徐春岳[1] 徐剑[2] 姚水洪[1] 

机构地区：[1]浙江省衢州职业技术学院医学院,324000 [2]浙江大学医学院附属第一医院肝胆胰外科

出　　处：《中华微生物学和免疫学杂志》2012年第3期239-244,共6页Chinese Journal of Microbiology and Immunology

基　　金：浙江省衙州市科技计划项目（20111081）

摘　　要：目的将大鼠胚胎胸腺与后肾原基联合移植至无胸腺裸小鼠，探讨联合移植能否重建受体细胞免疫功能并诱导受者对异种供者器官的特异性免疫耐受的关系。方法从受孕第15天（E15）的Lewis大鼠胚胎中提取胸腺、后肾原基，分别植入BALB／c裸小鼠腹腔右肾包膜下及大网膜内。移植后第10周，行胸腺、后肾移植物的形态学检查及移植后肾的功能检测；并进行外周血T淋巴细胞流式细胞学检测、单向混合淋巴细胞反应（MLR）及皮肤移植试验。结果移植后第10周，移植胸腺及后肾形态发育良好。移植后肾显示一定的排泄功能，联合移植受体双肾切除后的生存时间明显延长（P〈0．05）。联合移植受体的外周血T淋巴细胞重建良好；其淋巴细胞对胸腺供体来源的Lewis大鼠脾细胞的刺激呈特异性低反应（P〈0．01）；且胸腺供体来源的大鼠移植皮片平均存活时间明显大于C57BL／6小鼠、BN大鼠移植皮片存活时间（P〈0．01）。结论E15Lewis大鼠胚胎胸腺、后肾原基联合移植至细胞免疫缺陷的裸小鼠，移植物可生长分化形成器官并发挥功能，受体裸小鼠能重建免疫功能，并有可能诱导对同源供体器官的特异性异种移植免疫耐受。Objective To investigate whether the cellular immune function of athymia nude mice can be reestablished and whether the recipients＇ specific immune tolerance can be induced by the combined xenotransplantation of embryonic thymus and metanephros anlagen from rats to athymia nude mice. Methods Male and female rats were mated overnight. The presence of vaginal plaques was marked as the embryonic day 0（E0）. The whole embryos from Lewis rats on embryonic day 15（E15） were taken for the present experiment. The Lewis El5 metanephros and thymus anlagen were taken out from the embryos and immediately preserved in normal saline at 4℃, and then were implanted into the omentum and renal capsule of nude mice. 10 weeks post-implantation, the peritoneotomy was carried out on some recipients, metanephros and thymus transplants were removed for histopathological examination. The concentrations of urea nitrogen and creatinine in cyst fluid from the metanephros transplants were measured. The survival time of the recipients was observed after nephrectomy. The blood of the recipients was obtained to detect the re-establishment of T lymphocyte with flow cytometry（FCM）. The lymphocyte suspension extracted from recipients were mixed respectively with the spleen cells suspension of Lewis rats, BN rats or C57BL/6 mice to perform mixed lym- phocyte reaction（MLR） test. The skins of Lewis rats, BN rats, C57BL/6 and nude mice were transplanted in the chest-back of the recipients to observe the reject reaction. Results 10 weeks post-implantation, both El5 metanephros and thymus transplants were enlarged, and showed well-developed structure under optical microscope and electronic microscope. Metanephros displayed partial excreting function. The concentrations of urea nitrogen and creatinine in cyst fluid from the metanephros transplants were close to the concentrations in the bladder urine. The combined transplant recipients survived longer than the others after nephrectomy（P 〈0.05）. The re-establishment of T lymphocyte

关 键 词：胚胎 胸腺 后肾 移植 免疫耐受 

分 类 号：R392.1[医药卫生—免疫学]