共刺激阻断剂与雷帕霉素联合应用对移植胰腺存活的影响  

Influence of PD-L1Ig combined with rapamycin on the survival of pancreas allograft in rats

作　　者：于刚[1] 徐泽宽[1] 张轩[1] 曹晓飞[1] 苗毅[1] 

机构地区：[1]南京医科大学第一附属医院胆胰外科,南京210029

出　　处：《胰腺病学》2007年第6期391-393,共3页Chinese JOurnal of Pancreatology

基　　金：江苏省卫生厅135重点人才基金资助项目（苏卫科教[2003]19号）

摘　　要：目的探讨共刺激阻断剂PD-L1Ig与雷帕霉素（rapamycin,RPM）联合应用对大鼠移植胰腺存活的影响。方法以F344大鼠为供体,Lewis大鼠为受体,各40只。Lewis大鼠先注射链脲佐菌素制备成糖尿病模型,随后建立原位胰腺移植模型。随机分为移植组、PD-L1Ig治疗组（PD-L1Ig组）、RPM治疗组（RPM组）和PD-L1Ig＋RPM组（联合组）,观察各组术后血糖和移植胰腺病理改变、移植胰腺存活时间。移植后第7天各组处死2只大鼠,取受体与供体脾细胞做混合淋巴细胞反应（MLR）。结果移植后第1天血糖恢复正常,第7天移植组血糖较各治疗组明显升高（P〈0.01）,各治疗组中以联合组降糖效果最显著。PD-L1Ig组、RPM组的移植胰腺平均存活时间分别为（9.1±1.3）d和（12.5±1.2）d,较移植组的存活时间（5.2±0.7）d明显延长（P〈0.01）;联合组的存活时间则长达（23.9±1.8）d,与其他各组差异显著（P〈0.01）。移植后7d,PD-L1Ig组、RPM组移植胰腺有较多淋巴细胞浸润,联合组移植胰腺淋巴细胞浸润很少。结论PD-L1Ig与RPM联合应用可有效抑制细胞免疫应答,干预排斥反应,显著延长大鼠移植胰腺存活时间。Objective To investigate the role of costimulatory blockade PD-L1Ig combined with rapamycin on the survival of pancreas allograft in rats.Methods F344 →Lewis rat pancreas transplantation was performed.Experimental animals were randomly divided into four groups,10 rats for each.Group A（control）,group B（PD-L1Ig）,group C（RPM） and group D（PD-L1Ig ＋ RPM）.The overall survival of pancreas allograft,serum glucose of the recipients and the pathological changes of the allograft were measured.The mixed lymphocyte reaction（MLR） of the donor with the recipient spleen cells was performed.Results Significantly prolonged allograft survival time was observed in group B,C and D compared with that of the control group,and the longest survival was present in group D.The lowest serum glucose and fewest lymphocytes infiltrating grafts were also present in group D.The donor-specific MLR was suppressed in spleen cell cultures.Conclusions Combined use of PD-L1Ig and rapamycin（RPM） may suppress the cell-mediated immune responses and pancreas allograft rejection effectively and improve the survival of pancreas allograft.

关 键 词：胰腺移植 淋巴细胞培养试验 混合 雷帕霉素 共刺激阻断剂 

分 类 号：R587[医药卫生—内分泌]