新型HLA衍生肽延长异基因大鼠移植肾存活时间  

A novel HLA-derived peptide induces the immune tolerance of rats renal allografts

作　　者：易善红[1] 冯泉[2] 汪泽厚[2] 赵谦 叶钢[1] 

机构地区：[1]第三军医大学附属新桥医院泌尿外科,重庆400037 [2]解放军空军总医院泌尿外科 [3]解放军478医院泌尿外科

出　　处：《中华器官移植杂志》2005年第12期723-725,共3页Chinese Journal of Organ Transplantation

基　　金：国家新药基金资助项目(9690105184)

摘　　要：目的观察一种新型的人类白细胞抗原衍生肽(RDP1258)对大鼠肾移植后的免疫抑制作用。方法采用标准Fmoc法人工合成RDP1258。建立异基因大鼠原位肾移植模型。将已建立肾移植模型的大鼠随机分为4组,每组8只。A组:使用RDP1258+环孢素A(CsA);B组:单独使用RDP1258;C组:单独使用CsA;D组:不用任何药物。观察各组大鼠的存活时间,监测血清肌酐浓度,并进行移植肾彩色多普勒超声和常规病理检查。采用体外混合淋巴细胞反应(MLR)法检测长期存活大鼠的供者特异性免疫耐受状态。结果A、B、C和D组平均存活时间分别为(63.4±30.6)d、(18.3±7.3)d、(16.9±6.4)d和(9.4±2.6)d。A组与其他3组比较,差异有统计学意义。另外,混合淋巴细胞培养结果提示,长期存活的受者脾细胞对供者脾细胞的刺激不表现出明显细胞增殖反应,而对无关大鼠脾细胞仍能产生较明显的增殖反应。结论肾移植术后应用RDP1258结合小剂量CsA,能显著延长异基因大鼠移植肾存活时间,其机制可能与RDP1258诱导了受者对供者的特异性移植免疫耐受有关。Objective To observe the immunosuppression function of a novel HLA-derived peptide, RDP1258, after rat renal transplantation in vivo. Methods Peptides were synthesized by Fmoc chemistry method. The rat renal heterotopic transplantation model （n=32） was established. The allograft rats were divided into 4 group： group A （n=8） receiving subtherapeutic CsA＋RDP1258 peptide; group B （n=8） receiving RDP1258 alone; group C （n=8） receiving subtherapeutic CsA alone; and group D （n=8） receiving no immunosuppression. The renal allograft survival days of receptor rats were observed. Serum creatinine was measured and color Doppler flow imaging was checked. Renal tissues were harvested for light microscopic examination. The immunologic tolerance status of rat renal allografts was detected by MLR of 60th day receptor rat spleen cells cultured with the donor spleen cells and the third party. Results The allograft survival time in groups A, B, C and D were （63.4±30.6）days, （18.3±7.3）days, （16.9±6.4）days and （9.4±2.6）days, with the difference being significant between group A and other three groups. The results of MLR revealed that a hyporesponsiveness to donor occurred while the normal reaction to the third parity was retained. Conclusion A novel HLA derived peptide therapy combined with a sub-therapeutic dose of CsA significantly prolonged allograft survival days, and the mechanism might be that RDP1258 induced a donor-specific immunologic tolerance status in the recipients.

关 键 词：HLA 肾移植 免疫耐受 大鼠 

分 类 号：R699.2[医药卫生—泌尿科学]