CCR5反义肽核酸联合低剂量雷帕霉素对同种异体胰岛移植存活的影响  

Effect of combination of CCR5 anttsense peptide nucleic acid and Iose-dose rapamycin on islet aUograft survival

作　　者：杨蕾[1] 刘永锋[1] 李铁民[1] 赵国华[1] 程颖[1] 李弘[1] 

机构地区：[1]中国医科大学附属第一医院器官移植科,沈阳110001

出　　处：《中华微生物学和免疫学杂志》2007年第8期683-687,共5页Chinese Journal of Microbiology and Immunology

摘　　要：目的研究CCR5反义肽核酸(PNA CCR5)及联合应用低剂量雷帕霉素对同种异体胰岛移植急性排斥反应的影响。方法胰岛移植受体随机分4组:PNA CCR5组,低剂量雷帕霉素组(0.2 mg/kg),PNA CCR5联合应用低剂量雷帕霉素组,注射生理盐水组为对照组。监测术后IL-2、IFN-γ、IL-10 mRNA水平和CCR5蛋白水平,检测T淋巴细胞增殖能力。同时,移植物标本进行组织形态学观察。结果联合应用组与单独PNA CCR5组、低剂量雷帕霉素组相比,移植物存活时间明显延长(P<0.05)。与对照组相比,低剂量雷帕霉素组、单独PNA CCR5组和联合治疗组IL-2 mRNA表达水平降低(P<0.05,P<0.01)。联合应用组IL-10 mRNA水平较PNA CCR5组、低剂量雷帕霉素组升高,差异有统计学意义(P<0.01)。低剂量雷帕霉素组和联合应用组淋巴细胞增殖能力降低,同PNA CCR5组和对照组比较,差异均有统计学意义。结论PNA CCR5能够延长胰岛移植物存活时间,同时降低雷帕霉素用量,联合应用具有协同效应,进一步减轻排斥反应,延长胰岛移植物存活。Objective To investigate the effects of CCR5 antisense peptide nucleic acid （PNA） and the combination of PNA CCR5 and low-dose rapamycin on islet allograft acute rejection. Methods The recipient mice were divided into 4 groups： the PNA CCR5 group, the low-dose rapamycin group and the combination treatment group： the mice received PNA CCR5 and rapamycin at a dosage of 0.2 mg/kg per day, the saline group is a control. The mRNA levels of IL-2, IFN-γ and IL-10 of islet grafts were analyzed. CCR5 protein levels were evaluated by Western blot. T ceils proliferation was assessed by lymphocyte proliferation reaction. Histology of graft was eval- uated. Results The mean survival time of combination treatment allograft is longer than that of PNA CCR5 treatment （ P 〈 0.05） and low-dose rapamycin treatment allograft. At day 7 of transplantation, IL-2 mRNA expression of low-dose rapamycin, PNA CCR5 and combination treatment allograft were significantly down-regulated. PNA CCR5 increased mRNA expression of IL-10 （P 〈 0.05）, and this effect was accentuated by rapamycin （P 〈 0.01 ）. The mitogen-induced T cell proliferation was significantly down-regulated in low-dose rapamyein and combination treatment recipients. Conclusion PNA CCR5 can increase the survival time of islet allograft. Rapamyein can accentuate the role of PNA CCRS. The combination of PNA CCR5 and low-dose rapamycin further alleviates acute rejection and improves the survival of islet allograft.

关 键 词：胰岛 移植物排斥 CC趋化因子受体5(CCR5) 肽核酸(PNA) 雷帕霉素 

分 类 号：R657.51[医药卫生—外科学]