输注外源性白细胞介素13延长同种肝移植大鼠的存活时间

Infusion of exogenous recombinant interleukin-13 prolongs allograft survival in rat liver transplantation

目的探讨外源性重组白细胞介素13（rIL-13）抑制同种肝移植大鼠的排斥反应和延长大鼠存活时间的作用及其机制。方法以Lewis大鼠为供鼠，BN大鼠为受鼠，采用重建肝动脉的大鼠肝移植方法建立同种大鼠原位肝移植模型。采用随机数字表法将受鼠分为两组，实验组于术后第1、2、3、4和5天经尾静脉注射rIL-1310μg／d，同期对照组注射等体积生理盐水。术后第7天，检测两组移植肝功能，测定移植肝组织病理改变、细胞因子表达及CD8^＋T淋巴细胞浸润等情况，并根据Banff标准计算排斥活动指数（RAI），观察术后2周的存活率。结果与对照组相比，实验组肝功能明显改善，肝组织肿瘤坏死因子α（TNF-α）与E选择素的表达明显降低（P〈0．05），CD8^＋T淋巴细胞浸润明显减少（P〈0．05），术后2周存活率明显提高（P〈0．05）。实验组的RAI为4．8±1．2，明显低于对照组的7．5±1．2（P〈0．05）。结论外源性重组rIL-13可减少促炎症因子TNF-α释放和抑制E选择素的表达，减少移植物CD8^＋T淋巴细胞的浸润，从而减轻肝移植后急性排斥反应，延长大鼠的存活时间。

Objective To explore the effects of exogenous recombinant rat interleukin-13 （riL- 13） on the grafts in rat liver transplantation. Method The experiments were performed in a rat Lewis to Browta Norway acute reiection model of liver transplantation with arterial reconstruction. Exogenous rIL-13 （10 /,g） was injected into recipients via caudal vein on the day 1 to day 5 after transplantation in experimental group. In control group same volume of normal saline was injected. No additional irnmunosuppressive therapy was applied. The rats were sacrificed at 7th day. The levels of ALT and total billirubin （TB） in the serum, the expression levels of TNF-α, E-selectin, IFN-γ, IL4 and IL-10 mRNA in the grafts, and the infiltration of the CD8^＋ T cells in the grafts were detected. The 2 week survival rate of recipients was observed. Result As compared with control group, the levels of ALT and TB were decreased, the expression levels of TNF-α and E seiectin mRNA were down-regulated, the infiltration of CD8^＋ cells in the grafts was greatly inhibited, and the 2-week survival was significantly improved in the experimental group （P〈0. 05）. But there was no significant difference in the expression levels of IFN-7, IL-4 and IL10 mRNA between two groups （P〉0. 05）. Conclusion This study demonstrated that rlL-13 therapy significantly attenuated acute liver allograft damage and prolonged allograft survival through reducing the expression of the pro-inflammatory TNF-α and adhesion molecule E-selectin and limiting the infiltration of cytotoxic T ceils in the allograft.