转B、T淋巴细胞衰减子基因树突状细胞诱导大鼠肝移植免疫耐受的作用及机制  

Immune tolerance in liver transplantation induced by dendritic cells transfected with B and T lymphocyte attenuator gene in rats and its mechanism

作　　者：李军良[1] 郭天康[1] 张东[2] 黄军悦[3] 田宏伟[1] 王涛[1] LI Junliang;GUO Tiankang;ZHANG Dong;HUANG Junyue;TIAN Hongwei;WANG Tao(Department of General Surgery ,Gansu Provincial Hospital, Lanzhou 730030,China;Department of Medical Quality Control,Gansu Provincial Hospital, Lanzhou 730030,China;Department of Nephrology,Gansu Provincial Hospital, Lanzhou 730030,China)

机构地区：[1]甘肃省人民医院普通外科,甘肃兰州730030 [2]甘肃省人民医院医疗质量控制科,甘肃兰州730030 [3]甘肃省人民医院肾内科,甘肃兰州730030

出　　处：《中国普通外科杂志》2019年第1期70-76,共7页China Journal of General Surgery

基　　金：甘肃省青年科技基金资助项目(1606RJYA272)

摘　　要：目的:探讨慢病毒介导B、T淋巴细胞衰减子(BTLA)基因转染的树突状细胞(DC)诱导大鼠肝脏移植免疫耐受的作用及机制。方法:以DA大鼠为供体,为Lewis大鼠为受体,建立原位肝移植模型;获取SD大鼠DC后,分别用携带或不携带BTLA基因的重组慢病毒载体感染DC。将36只肝移植术后大鼠随机均分为模型组(移植术后无任何无处理)、DC组(肝移植术后输入未携带BTLA基因的重组慢病毒转染的DC)、BTLA-DC组(肝移植术后输入携带BTLA基因的重组慢病毒转染的DC)。每组术后7 d完成血生化指标与肝脏病理学检测后,剩余大鼠行生存时间分析。结果:与模型组比较,BTLA-DC组术后的肝功能损伤指标、免疫刺激细胞因子IFN-γ水平以及移植肝组织排斥反应的病理学评分降低,免疫抑制性细胞因子IL-10水平升高,但DC组术后的以上指标均呈一定程度的反向变化,定量指标的差异均有统计学意义(均P<0.05)。模型组的中位生存时间为15 d,DC组的中位生存时间为13 d,BTLA-DC组的中位生存时间为79 d,3组间的生存时间差异有统计学意义(χ~2=16.14,P=0.000 3)。结论:高表达BTLA的DC减缓了移植肝脏急性排斥反应,延长受体大鼠的生存时间,机制可能与其诱导T细胞免疫耐受有关。Objective: To investigate the immune tolerance in liver transplantation in rats induced by dendritic cells(DCs) transfected with B and T lymphocyte attenuator(BTLA) gene mediated by lentivirus and the mechanism.Methods: The animal models of orthotopic liver transplantation were established by using DA rats as donors and Lewis rats as recipient respectively. DCs were isolated from SD rats, and then were infected with recombinant lentivirus carrying or without BTLA gene, respectively. Thirty-six rats after liver transplantation were equally randomized into model group(without any treatment after liver transplantation), DC group(transfused with DCs without BTLA gene after liver transplantation) and BTLA-DC group(transfused with DCs bearing BTLA gene after liver transplantation). In each group of rats, after completion of serum biochemical tests and liver pathological examination on postoperative 7 d, the remaining rats were used for determining the survival time.Results: After transplantation, the liver function injury parameters, immune-stimulating cytokine IFN-γ level and rejection pathological score of the liver transplant were decreased and the immune-inhibiting cytokine IL-10 was increased in BTLA-DC group, but all above variables presented an opposite trend in DC group compared with model group, and the differences in all quantitative variables had a statistical significance(all P<0.05). The mean survival times for model group, DC group and BTLA-DC group were 15, 13, and 79 d respectively, and difference in survival time had statistical significance among the three groups(χ^2=16.14, P=0.000 3). Conclusion: DCs with high BTLA expression can alleviate rejection reactions of the liver transplant and prolong the survival time of the recipient rats, and the mechanism may possibly be associated with its inducing T cell immune tolerance.

关 键 词：肝移植 移植物排斥 树突细胞 免疫耐受 大鼠 

分 类 号：R657.3[医药卫生—外科学]