肝脏靶向表达趋化因子CXCL10 抑制ConA 诱导的肝脏损伤

目的:本研究探索趋化因子CXCL10 在免疫介导的肝脏损伤方面的作用及其作用机制。方法:尾静脉高压注 射CXCL10 表达载体72 h 后检测肝脏中CXCL10 的表达水平;再尾静脉注射刀豆蛋白(Concanavalin A,ConA)诱导免疫介导的 肝脏损伤;检测并比较CXCL10 表达组和对照组的谷丙转氨酶(Alanine aminotransferase,ALT)水平、组织损伤水平、,IFN-γ水 平、TNF-α水平及调节性T 细胞比例和数量的差异。结果:CXCL10 表达载体注射72 h 后,肝脏中CXCL10 的表达水平显著升 高;CXCL10 表达质粒预处理可以有效减轻ConA 诱导的肝脏损伤,CXCL10 表达组小鼠血清中的ALT 水平显著低于对照组, CXCL10 表达组小鼠血清中,IFN-γ和TNF-α的水平明显低于对照组,CXCL10 表达组小鼠肝脏中调节性T 细胞比例和数量高 于对照组。结论:趋化因子CXCL10 表达载体预处理可减少炎性细胞因子并减轻ConA 诱导的肝脏损伤,对治疗免疫介导的肝 炎具有重要意义。

Liver-targeted expression of chemokine CXCL10 inhibits ConA-induced liver in jury

Objective:To explore the effect and mechanism of CXCL10 on immune.mediated liver injury.Methods:The CXCL10 expression vector was injected into mice by hydrodynamic injection.The levels of CXCL10 in the liver were measured 72 hours after injection.Concanavalin A (ConA) was injected into mice to induce immune-mediated liver injury.The levels of alanine a mino- transferase (ALT),tissue damage,IFN-γ,TNF-α and percentages and numbers of regulatory T cells were tested and compared between CXCL10 expression group and control group.Results:The levels of CXCL10 in the liver were significantly increased at 72 hours after CXCL10 expression vector was injected.The pretreatment of CXCL10 expression vector markedly reduced ConA-induced ALT levels, IFN-γ levels and TNFα levels.Additionally,the pretreatment of CXCL10 expression vector increased the percentages and numbers of regulatory T cells in the liver.Conclusion:The pretreatment of CXCL10 expression vector decreases the levels of inflammatory cytokines and attenuates ConA-induced liver injury,which might be beneficial for the treatment for immune-mediated liver injury.