荣肝合剂对慢性免疫性肝损伤小鼠的保护作用

目的探讨荣肝合剂对刀豆蛋白A（ConA）介导的慢性免疫性肝损伤小鼠的保护作用及其机制。方法 HBV转基因小鼠69只,随机分为正常对照组10只（尾静脉注射PBS）和ConA造模组59只,采用ConA尾静脉注射造模制作慢性免疫性肝损伤模型。造模结束后,将所有ConA造模组小鼠随机分为模型组、荣肝合剂组、茵陈组、茵陈蒿汤组及联苯双酯组;正常对照组与模型组给予蒸馏水灌胃,各给药组小鼠每日灌胃给予相应的药物,各组均干预28天。末次灌胃给药后24h处死动物,取血或组织标本检测丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆红素（TBiL）、超氧化物歧化酶（SOD）、丙二醛（MDA）、肿瘤坏死因子α（TNF-α）、干扰素γ（INF-γ）、白介素-4（IL-4）、白介素-10（IL-10）等指标。结果模型组各指标与正常对照组比较,差异均有统计学意义（P〈0.05,P〈0.01）。与模型组比较：荣肝合剂组、联苯双酯组小鼠ALT、AST、TBiL水平显著降低（P〈0.01）;荣肝合剂组、茵陈蒿汤组和联苯双酯组肝组织中SOD水平均明显提高（P〈0.01）,荣肝合剂组、茵陈组肝组织中MDA水平明显降低（P〈0.05）;荣肝合剂组肝组织TNF-α和IFN-γ水平降低,IL-4、IL-10水平升高（P〈0.05,P〈0.01）。同时,荣肝合剂组降ALT、AST作用优于茵陈组、茵陈蒿汤组（P〈0.05）;提高SOD水平较茵陈组、茵陈蒿汤组、联苯双酯组显著（P〈0.01）;降低IFN-γ表达较茵陈组与联苯双酯组显著（P〈0.05,P〈0.01）。结论荣肝合剂对刀豆蛋白所致HBV转基因小鼠慢性免疫性肝损伤具有保护作用,其保护作用是通过调节肝细胞膜脂质过氧化反应水平（抑制MDA、提高SOD）和改变Th1/Th2因子平衡（降低TNF-α、IFN-γ的表达,提高IL-10、IL-4表达）而起作用的。

Protective effects of Ronggan Mixture on immunological chronic liver injury in mice

Objective To investigate the protective effects of ＂Ronggan Mixture＂ on immunological chronic liver injury in mice induced by concanavalin A（ConA）and its mechanisms.Methods HBV transgenic mice were randomly divided into normal group（10）and ConA model group（59）.The normal group was given PBS by the tail vein injection（0.3 ml）,while the others were given ConA by the tail vein injection（6 μg/g）;8 weeks after the modeling,the ConA-induced mice were devided into model group,＂Ronggan Mixture＂ group,Yinchen group,Yinchenhao Decotion group and Bifendate group.Then the mice were gastrically perfused with corresponding therapeutic interventions for 4 weeks,while the normal group and model group were given normal saline.Twenty-four hours after the last gastric perfusion,the mice were sacrificed,then the serum and tissue samples were collectd to detect various indicators：ALT,AST,TBIL,SOD,MDA,TNF-α,INF-γ,IL-4 and IL-10.Results Significant differences were found in all indicators between normal group and model group（P0.05 or P0.01）.Compared with the model group,the indicators of ALT,AST and TBIL were significanly lower in ＂Ronggan Mixture＂ group and Bifendate group（P0.01）;the level of SOD in the liver increased after the intervention of the ＂Ronggan Mixture＂,Yinchenhao Decotion and Bifendate（P0.01）;while ＂Ronggan Mixture＂ and Yinchen solution could decrease the level of MDA（P0.05）;＂Ronggan Mixture＂ could decrease the level of TNF-α and IFN-γ,and increase the level of IL-4 and IL-10 in the liver tissue（P0.01 or P0.05）.Meanwhile,the effect of lowering ALT and AST in ＂Ronggan Mixture＂ group was superior to Yinchenhao Decotion group and Yinchen group（P0.05）;＂Ronggan Mixture＂ had better effect in increasing SOD than Yinchenhao Decotion,Yinchen solution and Bifendate（P0.01）;compared with Yinchen group and Bifendate group,＂Ronggan Mixture＂ could obviously lower the expression of IFN-γ in liver tissue（P0.05 or P0.01）.Conclusion The ＂Ronggan Mixture＂ has protective effect on chronic immunological liver injury in mice induced by ConA by blocking the lipid peroxidation of hepatocyte and regulating the balance of Th1/Th2 ceu factors level.