新型衍生肽对淋巴细胞免疫功能及大鼠异基因移植肾存活的影响  

Effects of a novel derived peptide on the immune function of lymphocyte and survival of rats renal allograft

作　　者：易善红[1] 汪泽厚[2] 叶钢[1] 黄赤兵[1] 张艮甫[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

出　　处：《中华泌尿外科杂志》2007年第4期253-256,共4页Chinese Journal of Urology

基　　金：国家新药基金资助项目（9690105184）

摘　　要：目的 探讨新型组织相容性白细胞抗原（HLA）衍生肽RDPI258对淋巴细胞免疫功能及大鼠移植肾脏存活时间的影响。方法 采用人工标准固相合成法合成HLA衍生肽RDP1258，^3H—TdR掺入法观察其在体外对人外周单核细胞增殖反应的影响。建立原位大鼠异基因肾移植模型32只，设RDP1258＋CsA治疗组、RDP1258治疗组、CsA治疗组及对照组4组，每组8只，观察大鼠移植肾脏存活时间及移植肾功能。结果RDP1258可显著抑制淋巴细胞转化及单向混合淋巴细胞增殖反应（MLR）；RDP1258＋CsA治疗组受体大鼠平均存活63．4d，对照组平均存活9．4d，CsA治疗组平均存活16．9d，RDP1258治疗组平均18．3d，各组与联合治疗组比较差异有统计学意义（P〈0．05）。对照组在术后5d切除对侧肾脏后血清肌酐浓度（450．0±84．2）μmol／L，CsA及RDP1258组血清肌酐浓度呈现缓慢上升趋势，分别为（360．0±78．4）及（350．0±65．8）μmol／L，与联合治疗组（47．4±11．2）μmol／L相比，差异有统计学意义（P〈0．05）。结论 RDP258能显著抑制人外周单核细胞丝裂原或同种抗原刺激引起的增殖反应，围手术期应用HLAⅠ类分子衍生肽结合小剂量CsA，能显著延长异基因移植物存活时间及功能，RDP1258可能成为一种新型的器官移植免疫调节药物。Objective To investigate the effects of a novel HLA-derived peptide, RDP1258 on lymphocyte immune function and suvival of rat renal allograft. Methods Peptides were synthesized by Fmoc chemistry method. The effects of the peptide on alloreactive cytotoxic activities of Human peripheral blood mononuclear cells were observed using ^3 H-TdR incorporation method. The model of orthotopic transplantation rat renal allograft into abbominal was established. Thirty-two F344 rats underwent unilateral nephrectomy and heterotopic transplantation with a LEW kidney. Group 1 （n= 8） received no immunosuppression, group 2 （n=8） received subtherapeutic CsA alone, group 3 （n= 8） received RDP1258 alone, group 4 （n=8） received subtherapeutic CsA＋RDP1258 peptide. The renal allograft survival days of receptor rats were observed. Serum creatinine was measured every week. Results The results showed that the synthetic HLA-derived peptide can obviously inhibit the proliferation of Human peripheral blood mononuclear cells. The allograft survival of peptide therapy combined with a subtherapeutic dose of CsA （63.4 days） was prolonged significently compared with the control group （9.4 days）, peptide RDP1258 along （18.3 days）, CsA along （16.9 days） （P〈0.05）. It also reflected in significantly lower serum creatinine levels （47. 4 ± 11.2 μmol/L） compared with control group （450.0±84.2 mmol/L）, RDP1258 along （350.0 ± 65.8 μmol/L）, CsA along （360.0 ± 78. 4 μmol/L）（P〈0.05）. Conclusions RDP1258 can inhibit the proliferation of Human peripheral blood mononuclear cells. RDP1258 therapy combined with a sub-therapeutic dose of CsA can significantly prolong allograft survival. RDP1258 could be adopted as a novel immunomodulatory drug to treat the transplantation rejection.

关 键 词：肾移植 免疫 细胞 动物 实验 

分 类 号：R686[医药卫生—骨科学]