雷帕霉素联合IL-2融合蛋白在小鼠皮肤移植模型中对乙肝疫苗免疫原性的影响  

Immunogenicity of HBV vaccine influenced by combined rapamycin and IL-2 fusion protein in a mouse skin transplantation model

作　　者：李照[1] 高杰[1] 李涛[1] 朱继业[1] 

机构地区：[1]北京大学人民医院肝胆外科 北京大学器官移植中心,100044

出　　处：《中华普外科手术学杂志（电子版）》2012年第4期47-50,共4页Chinese Journal of Operative Procedures of General Surgery(Electronic Edition)

基　　金：国家973课题资金资助项目(2009CB522403)

摘　　要：目的研究雷帕霉素联合IL-2融合蛋白对小鼠皮肤移植术后乙肝疫苗免疫原性的影响,寻求移植术后预防乙型肝炎的有效方法。方法 DBA小鼠为供体,C57BL/6小鼠为受体,行皮肤移植后分为联合治疗组、雷帕霉素组、疫苗组,每组10只,联合治疗组给予雷帕霉素(1mg/kg,腹腔内注射)+IL-2融合蛋白(1μg/只,腹腔内注射)+疫苗;雷帕霉素组只给予雷帕霉素+疫苗;疫苗组仅给予乙肝疫苗。以上3组均在皮肤移植后第一天给予乙肝疫苗(2μg/只,肌肉注射)。空白组不给于任何处理。14d后测定各组血清中乙肝抗体滴度水平、IL-4、IL-10、IL-2、IFN-γ水平,应用RT-PCR测定各组淋巴组织中IL-21、FoxP3及Bcl-6的表达水平,同时随访小鼠皮肤移植物存活时间。结果联合治疗组移植术后乙肝表面抗体(HBsAb)滴度明显高于雷帕霉素组(P<0.05),皮肤移植物的存活时间也明显延长(P<0.05);联合治疗组Th2类因子IL-4,IL-10的水平明显低于雷帕霉素组(P<0.05),而Th1类因子IL-2和IFN-γ水平明显较高(P<0.05)。联合治疗组混合淋巴细胞中IL-21、FOXP3的表达水平明显高于雷帕霉素组(P<0.05),而Bcl-6的表达水平明显较低(P<0.05)。结论雷帕霉素联合IL-2融合蛋白联合应用能够在移植术后增强乙肝疫苗产生抗体的滴度,同时延长移植物的存活时间,为临床移植术后提高疫苗免疫原性提供了一种治疗策略。Objective To investigate the effect of rapamycin and IL-2 fusion protein on immunogenicity of HBV vaccine and to explore an effective way to prevent HBV recurrence after liver transplantation.Methods The experimental animals were divided into control group（n=10）,vaccine group（n=10）,Rapa group（n=10）,and Rapa＋IL-2/Fc group（n=10）.C57BL/6 and DBA/2 mice were used as recipients and donors respectively.In each group,C57BL/6 mice received skin grafts of DBA/2 mice,then C57BL/6 mice were given Rapa（1mg/kg,intraperitoneal） and/or IL-2/Fc（1 μg,intraperitoneal） and/or HBV vaccine（2 μg,intramuscular） was injected respectively on indicated days after operation.On day 14 after skin transplantation,the serum levels of HBSAb,IL-4,IL-10,IL-2 and IFN-γ were measured by ELISA,while the mRNA level of IL-21,Foxp3 and Bcl-6 were measured by RT-PCR in lymph tissue and the survival rates of skin grafts were recorded.Results The HBSAb level in the Rapa＋IL-2/Fc group was significantly higher than that in the Rapa group（P0.05）.Compared to the Rapa group,the survival of skin graft in the Rapa＋IL-2/Fc group was also prolonged（P0.05）and Th1 cytokines such as IL-2,IFN-γ were significantly increased（P0.05）.Th2 cytokines such as IL-4 and IL-10 were decreased significantly（P0.05）in the Rapa＋IL-2/Fc group.Compared to the Rapa group,IL-21 and Foxp3 expressions were significantly up-regulated（P0.05）,while Bcl-6 expression was down-regulated（P0.05）in the Rapa＋IL-2/Fc group.Conclusions Combined treatment with Rapa and IL-2/Fc could significantly enhance the immunogenicity of HBV vaccine and prolong graft survival.The treatment provides a potential therapeutic strategy to enhance the immunogenicity of vaccine after transplantation.

关 键 词：西罗莫司 肝炎疫苗 乙型 T淋巴细胞 辅助诱导 皮肤移植 疾病模型 动物 

分 类 号：R622.1[医药卫生—整形外科] R-332[医药卫生—外科学]