CAJ | 학술논문

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-13 10μg/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的释放和抑制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.
목적 탐토외원성중조백세포개소13(rIL-13)억제동충간이식대서적배척반응화연장대서존활시간적작용급기궤제.방법 이Lewis대서위공서,BN대서위수서,채용중건간동맥적대서간이식방법건립동충대서원위간이식모형.채용수궤수자표법장수서분위량조,실험조우술후제1、2、3、4화5천경미정맥주사rIL-13 10μg/d,동기대조조주사등체적생리염수.술후제7천,검측량조이식간공능,측정이식간조직병리개변、세포인자표체급CD8+T림파세포침윤등정황,병근거Banff표준계산배척활동지수(RAI),관찰술후2주적존활솔.결과 여대조조상비,실험조간공능명현개선,간조직종류배사인자α(TNF-α)여E선택소적표체명현강저(P＜0.05),CD8+T림파세포침윤명현감소(P＜0.05),술후2주존활솔명현제고(P＜0.05).실험조적RAI위4.8±1.2,명현저우대조조적7.5±1.2(P＜0.05).결론 외원성중조rIL-13가감소촉염증인자TNF-α적석방화억제E선택소적표체,감소이식물CD8+T림파세포적침윤,종이감경간이식후급성배척반응,연장대서적존활시간.
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 Brown Norway acute rejection model of liver transplantation with arterial reconstruction.Exogenous rIL-13 (10 μg) 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 immunosuppressive 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,IL-4 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-selectin 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-γ,IL-4 and IL-10 mRNA between two groups (P＞0.05).Conclusion This study demonstrated that rIL-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 cells in the allograft.