T细胞分化群40补体免疫球蛋白基因修饰骨髓间充质干细胞在肝移植排斥反应中的作用  

Effects of CD40LIg gene-modified bone marrow mesenchymal stem cells on liver graft rejection in rats

作　　者：张剑[1] 张琪[1] 汪国营[1] 张英才[1] 朱焕兵[1] 杨扬[1] 

机构地区：[1]中山大学第三医院器官移植科,广东广州510630

出　　处：《南方医科大学学报》2011年第11期1903-1906,共4页Journal of Southern Medical University

基　　金：国家自然科学基金(81070382);广东省科技计划项目(2008B030301050)~~

摘　　要：目的探讨T细胞分化群40补体免疫球蛋白(CD40LIg)基因修饰骨髓间充质干细胞(MSCs)肝移植排斥反应中的作用。方法采用双袖套法建立DA-Lewis大鼠原位肝移植模型,经门静脉输注CD40LIg基因转染的MSCs,观察大鼠肝移植术后肝功能的变化、生存情况和移植肝病理形态学的改变,检测肝移植大鼠干扰素(INF-γ)和白细胞介素4(IL-2)水平的变化。结果(1)基因转染MSCs组生存时间显著长于对照组、单纯MSCs组和基因转染组,而单纯MSCs组和基因转染组又较对照组显著延长(P<0.05)。(2)对照组谷丙转氨酶(ALT)、总胆红素(TBil)、IL-2和INF-γ水平在肝移植术后急剧升高,各时段均显著高于3个治疗组(P<0.05);(3)肝脏组织病理检查,对照组呈重度排斥反应,单纯MSCs组和基因转染组为轻度排斥反应,而基因转染MSCs组无明显排斥反应。结论 CD40LIg基因修饰MSCs可以延长肝移植大鼠的存活时间,抑制大鼠肝移植的排斥反应。Objective To study the effects of cluster of differentiation 40 ligand immunoglobulin（CD40LIg） gene-modified bone marrow mesenchymal stem cells（MSCs） on liver graft rejection in rats.Methods The orthotopic liver transplantation models were established with DA rats as the donors and Lewis rats as the recipient.MSCs infected with the recombinant adenoviruses containing CD40LIg gene were infused into the liver graft after transplantation.The liver function,survival of the recipient rats and the morphological changes of the liver grafts were observed after the transplantation.The serum levels of the cytokines interferon-γ（INF-γ） and interleukin-2（IL-2） in the recipient rats were quantified by ELISA.Results The survival of the recipient rats receiving transplantation of genetically modified MSCs（group D） was significantly prolonged compared with that of the control group（group A）, MSCs group（group B） and gene transfection group（group C）;the survival of groups B and C were significantly longer than that of group A（F=7.615,P0.05）.The level of serum alanine aminotransferase,total bilirubin,IL-2 and INF-γ were significantly higher in group A than in the other 3 groups（F=8.738,P0.05）.HE staining of the liver grafts showed severe acute rejection in group A,mild acute graft rejection in groups B and group C,but no rejection in group D.Conclusion CD40LIg gene-modified MSCs can prolong the survival of the recipient rats and suppress graft rejection following liver transplantation.

关 键 词：骨髓间充质干细胞 T细胞分化群40补体免疫球蛋白 肝脏移植 基因修饰 排斥反应 

分 类 号：R657.3[医药卫生—外科学] R33[医药卫生—临床医学]