腺病毒介导CD40Ig基因在大鼠肝脏移植中的作用

Role of CD40Ig Mediated by Adenovirus in Rats Liver Transplantation

目的探讨腺病毒介导CD40Ig基因(AdCD40Ig)在大鼠肝脏移植中的作用。方法随机将供受体大鼠分4组,A:同基因移植组,B:免疫排斥组,C:AdLacZ对照组,D:基因治疗组。观察大鼠存活时间,CD40Ig、细胞因子水平和移植肝病理情况。结果 D组存活时间长于B、C组(P<0.05);CD40Ig浓度于术后7天达高峰;D、A组IL-2、IFN-γ水平较B、C组明显降低(P<0.05),D组IL-10较其他组明显增加(P<0.05);B、C两组术后出现中、重度排斥反应,汇管区淋巴细胞浸润明显,D组汇管区轻度炎症,无明显血管损伤证据,病理评级较B、C组有统计学意义(P<0.05)。结论 CD40Ig通过阻断CD40/CD40L通路,可延长移植肝存活时间,在受体内长期表达,减少汇管区淋巴细胞浸润,影响相关细胞因子的表达,对大鼠肝脏急性排斥反应有抑制作用。

Objective To investigate the role of CD40Ig mediated by adenovirus in rats liver transplantation. Methods The rats were divided into four groups at random. A was control group; B was Lewis→BN; C was AdLacZ control group; and D was AdCD40Ig group. The survival time, the level of CD40Ig, cytokines, stimulation index of the MLR and pathological changes were observed. Results The recipients in group D got a long - time survival （53.25±13.38days, P 〈 0.05 vs. group B and group C）. The level of CD40Ig was the highest on day 7 after transplantation. The IL - 2 and IFN - γ in group A and D were lower than that in control groups （ P 〈 0.05） , but had the opposite result in IL - 10. The moderate to severe responses was observed in both group B and C ,and the infiltrations of inflammatory cells in portal areas were also detected. In contrast, group D had a mild periportal inflammation and tissue injuries. Con- clusion The CD40Ig could be effectively transduced and expressed into the allograft for a longer time. It could not only reduce infiltra- tions of lymphocyte, intervene the expression of Th - associated cytokine, but also prolong the survival time of the liver allograft by bloc- king CD40/CD40L.