甘草酸铵通过抑制HMGB1的表达减轻ConA诱导的免疫性肝损伤

Glycyrrhizin ameliorates ConA-induced liver injury by inhibition of high-mobility group box 1 in mice

目的探讨甘草酸铵对刀豆蛋白A(Concanavalin A,ConA)诱导的免疫性肝损伤的保护作用及其可能的分子机制。方法在小鼠尾静脉注射ConA(20 mg/kg)前30 min,腹腔注射甘草酸铵(100 mg/kg)。ConA注射后8 h,检测血清转氨酶水平及肝组织学以评估肝损伤程度,应用酶联免疫法(ELISA)检测肝组织肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)、白介素-10(IL-10)水平。同时,分别采用实时荧光定量PCR和免疫组化检测肝组织高迁移率族蛋白-1(HMGB1)mRNA与蛋白的表达。结果预防性应用甘草酸铵有效地保护ConA诱导的小鼠免疫性肝损伤,表现为血清转氨酶水平与肝脏组织炎症坏死程度明显减轻;与ConA模型组相比,甘草酸铵对肝脏内的促炎症细胞因子TNF-α和IFN-γ并无影响,但增加了抗炎症因子IL-10水平(P<0.01);同时,甘草酸铵预防组肝组织HMBG1基因与蛋白的表达均明显低于模型组(P均<0.01)。结论甘草酸铵有效改善ConA诱导的小鼠免疫性肝损伤,其发挥作用的分子机制与抑制HMBG1表达有关。

Objective To examine the hepatoprotective effect and the potential molecular mechanism of glycyrrhizin（ammonium salt） on Concanavalin A（ConA）-induced hepatitis in mice. Methods Mice received glycyrrhizin by intraperitoneal injection before 30 minutes ConA intravenous administration.The liver injury was examined by measuring serum transaminase and liver histology 8h after ConA injection,and the tumor necrosis factor（TNF）-α,interferon（IFN）-γ,and interleukin（IL）-10 levels in liver tissue were detected by enzyme linked immunosorbent assay（ELISA）.Furthermore,the expression of high-mobility group box 1（HMGB1） mRNA and protein in liver was detected by Real-time quantitative PCR and immunohistochemical staining,respectively. Results The treatment of mice with glycyrrhizin before ConA injection significantly reduced the elevated plasma levels of aminotransferases and the incidence of liver necrosis compared with ConA-injected control group.ELISA showed that glycyrrhizin had no effect on the production of TNF-α and IFN-γ in the liver,whereas it significantly increased the IL-10 production compared with the saline-treated controls.Furthermore,the expression levels of HMGB1 mRNA and protein in the liver were significantly lower（P0.01） in glycyrrhizin-treated mice. Conclusion Glycyrrhizin pretreatment protects against ConA-induced liver injury in mice.The beneficial effect may inhibit HMGB1 expression.