针对OX40小干扰RNA供体转染抗大鼠肝移植排斥反应  

Prolonging rat liver allograft survival by blockade of OX40-OX40L co-stimulatory signaling

作　　者：夏仁品[1] 卢实春[1] 赖威[1] 戴军[1] 娄金丽[2] 李宁[1] 

机构地区：[1]首都医科大学附属北京佑安医院外科,北京100069 [2]北京市卫生局肝炎研究所北京市

出　　处：《中华实验外科杂志》2008年第7期860-862,共3页Chinese Journal of Experimental Surgery

基　　金：2007年教育部留学回国人员科研启动基金资助项目;首都医科大学基础与临床合作基金资助项目（2006JL55）

摘　　要：目的观察RNA干扰阻断OX40-OX40L共刺激通路对大鼠移植肝存活时间的影响。方法制作DA大鼠到Lewis大鼠的原位肝脏移植模型，移植前取预先制备的5ml含5×10^9pfu的pLVTHM-OX40-siRNA重组慢病毒，灌注感染移植供肝30min，术后观察受者存活时间，移植肝脏进行组织病理学检查；采用ELISA法检测大鼠外周血IL-2，IFN-γ的水平，并进行受者大鼠脾细胞对供者大鼠脾细胞的混合淋巴细胞反应（MLR）。结果转染组受者肝脏移植物的存活时间为（74．00±3．79）d，明显长于对照组和未转染组；转染组移植肝组织炎细胞侵润、间质水肿、肝组织坏死程度较对照组和未转染组减轻，实验组大鼠脾细胞刺激T淋巴细胞增殖的能力降低（P〈0．01）；移植术后的第7天，转染组血清IL-2浓度为（46．0±8．4）ng／L，IFN-γ浓度为（202．7±14．6）ng／L，均显著低于对照组和未转染组（P〈0．05）。结论转染靶向OX40的siRNA，在体内可通过阻断OX40-OX40L共刺激通路，抑制大鼠肝脏移植后的排斥反应，延长大鼠移植肝的存活时间。Objective To investigate the effect of blockade of OX40-OX40L co-stimulatory signal on the survival time of rat liver allograft. Methods siRNA-expression vectors were constructed to target OX40. Heterotopic liver transplantation models in rats were established. Liver allografts were infected by in situ peffusion of viral particle （5 x 10^9 pfu of pLVTHMOX40siRNA） perioperatively. Histological examination was done, Serum IL-2 and IFN-γ levels were assayed by ELISA, and mix lymphocyte response （MLR） was tested by 3 H-thymidine. Results The survival time of recipients in siRNA treatment group （74.00 ±3.79） days was significantly longer than that in control group （7.33 ±0.21 ） days,P 〈0.01. The inflammatory cell infiltration and liver tissue structure destruction were very milder in siRNA treatment group than in control group. The concentrations of serum IL-2 and IFN-3, were （ 46 ± 8.4） ng/L and （202.7 ± 14.6） ng/L in siRNA treatment group, which were significantly lower than in control group （286.5 ±14.6） ng/L and （1682.7 ±87.9） ng/L respectively （all P〈0.05）. Conclusion Administration of OX40 siRNA can block OX40-OX40L eo-stimulatory signal and inhibit the rejection of liver allograft,so as to prolong the survival time of the grafts after transplantation.

关 键 词：器官移植 OX40 小干扰RNA 肝脏 

分 类 号：R657.3[医药卫生—外科学]