BTLA负性共刺激分子修饰树突状细胞对大鼠移植肝脏的免疫保护作用  

Immunoprotection of BTLA negative co-stimulatory molecule modified dendritic cells in rat liver transplantation

作　　者：马毅[1] 叶智明[1] 李彦杰[1] 

机构地区：[1]中山大学附属第一医院器官移植中心,广州510080

出　　处：《中华实验外科杂志》2011年第8期1327-1330,共4页Chinese Journal of Experimental Surgery

基　　金：基金项目：广东省自然科学基金资助项目（9151008901000052）;广东省科技计划资助项目（20108031600216）

摘　　要：目的探讨BTLA修饰的树突状细胞（DC）对肝脏移植物免疫保护的诱导作用及机制。方法72只大鼠肝移植免疫排斥模型（选择DA大鼠36只为供体，Lewis大鼠36只为受体），随机分为3组：A组（非干预组，n=12）移植术后不用免疫抑制剂；B组（FKS06处理组，n=12）术后用FKS060．2mg／（kg·d）灌胃；C组（BTLA干预组，n=12；即经重组腺病毒Adv—BTLA修饰的DC回输组）。分别于术后3、5、7d随机解剖受体大鼠6只，取材肝组织对移植肝进行病理学观察，同时静脉采血测定血清谷丙转氨酶（ALT）、白蛋白（ALB）和总胆红素（TBIL）浓度；每组各留6只观察其生存时间和死亡原因。结果A组的DA→Lewis组合的模型术后血清生化指标、肝脏病理学改变、生存情况均符合肝移植急性排斥的特点，排斥反应于术后3—5d出现，并逐渐增强，术后7d迅速达到高峰并维持；B组急性排斥可以为免疫抑制药物FK506预防而达到长期存活；C组急性排斥程度明显减轻，且排斥反应出现时间要晚，受体大鼠存活时间明显延长。A、B和C组中位生存时间分别为14、73、26d；3组的累积生存率曲线差异有统计学意义（Log—Rank取值为19．13，P〈0．01）。结论BTLA修饰的DC可以对大鼠移植肝脏起到免疫保护作用；经BTLA修饰的供体DC细胞迁移到受体组织内，能够抑制肝移植急性排斥反应，并延长移植肝和受体大鼠存活时间。Objective To explore the induction and mechanisms of immuoprotective effect on liver grafts by B and T lymphocyte attenuator （BTLA） modified dendritic cells （DCs）. Methods Immunological rejection model was established： 72 rats （36 pairs： 36 DA rats as donors, and 36 Lewis rats as recipients） were randomly divided into 3 groups： group A （control group,n = 12）, with no immunosuppressive regimen ; group B ： （ FKS06 treatment group, n = 12） , intra-gastric administration of FKS06 （0. 2 mg/kg. day） ; group C （BTLA intervention group,n = 12, transfusion of adenovirus-BTLA modified DCs to the recipients）. Six rats from each group were chosen randomly and sacrificed on the operative day 3, 5, 7 respectively. Liver biopsy was subjected to pathological examination, and blood alanine aminotransferase （ALT）, albumin and total bilirubin were determined. Six rats in each group were kept to explore the survival time and the reasons of death. Results Group A： All indicators including biochemical parameters, pathologic changes, and survival time suggested acute rejection. The indications of acute rejection emerged on the day 3 to day 5, and got stronger with time, finally reached a peak on the day 7, and maintained the levels. Group B： Rejection-free long-term survival was achieved due to the application of FKS06. Group C： Acute rejection was much less serious and occurred later than in group A, and the survival time prolonged significantly. The mean survival time in groups A, B and C was 14, 73, and 26 days, respectively, and there was statistically significant difference among three groups （ Log-Rank = 19. 13, P 〈 0. 01 ）. Conclusion In rat liver transplantation, BTLA modified DCs derived from the donors migrate into recipients, and depress acute immunological rejection, thus prolonging the survival time of grafts and recipients.

关 键 词：肝移植 BTLA 免疫保护 

分 类 号：R657.3[医药卫生—外科学]