扶正祛邪方抗ConA模型小鼠肝损伤的作用机制

Mechanism of Fuzheng Quxie Prescription Against Liver Injury of Con A Model Mice

目的:探讨扶正祛邪方通过对刀豆蛋白A(Con A)模型小鼠肝组织中肿瘤坏死因子-α(TNF-α),凋亡因子(Fas),凋亡因子配体(Fas L),巨噬细胞(CD68)表达的影响从而发挥对肝损伤的保护作用。方法:将60只小鼠随机分为正常组、模型组、双环醇组(62. 5 mg·kg-1)、扶正祛邪方低、中、高剂量组(50. 3,67. 0,83. 8 g·kg-1)。正常组和模型组给予等体积纯水,连续7 d。末次给药前禁食12 h,给药2 h后,正常组尾静脉注射磷酸盐缓冲液(PBS),其余各组尾静脉注射Con A(20 mg·kg-1)造模。注射6 h后取材,免疫组化观测肝组织中TNF-α,Fas L,CD68表达情况。结果:与正常组比较,模型组肝组织中TNF-α,Fas,Fas L,CD68表达均显著升高(P <0. 01),说明肝损伤模型复制成功;与模型组比较,双环醇组肝组织中TNF-α,Fas L,CD68表达均显著降低(P <0. 01);扶正祛邪方中、高剂量组肝组织中TNF-α,Fas,Fas L,CD68表达均显著降低(P <0. 05,P <0. 01)。结论:扶正祛邪方可通过抑制Kupffer细胞和Fas/Fas L系统的活化,有效减少Con A模型小鼠肝细胞凋亡。

Objective:To study the protective effect of Fuzheng Quxie prescription on liver injury by influencing the expressions of tumor necrosis factor(TNF)-α,apoptosis factor(Fas),apoptosis factor ligand(FasL),and macrophages(CD68)in the liver tissues of concanavalin A(ConA)model mice.Method:The sixty mice were randomly divided into normal group,model group,bicyclol group(62.5 mg·kg-1),and low,medium and high-dose Fuzheng Quxie prescription groups(50.3,67.0,83.8 g·kg-1).The normal group and the model group were given the equal volume of pure water for 7 d.They were fasted for 12 hours before the last administration.At 2 ndhour after the last administration,phosphate buffer(PBS)was injected into the caudal vein of the normal group,and ConA(20 mg·kg-1)was injected into the caudal vein of the other groups for modeling.The animals were put to death six hours later after the injection,and the expressions of TNF-α,Fas,FasL and CD68 in liver tissues were observed by immunohistochemistry.Result:Compared with normal group,the expressions of TNF-α,Fas,FasL and CD68 in the liver tissues of the model group were significantly increased(P<0.01),indicating the successful replication of the liver injury model.The expressions of TNF-α,FasL and CD68 in liver tissues of the bicyclol group were significantly decreased compared with the model group(P<0.01).The expressions of TNF-α,FasL and CD68 in liver tissues were significantly decreased in medium and high-dose Fuzheng Quxie prescription groups(P<0.05,P<0.01).Conclusion:Fuzheng Quxie prescription can effectively reduce the apoptosis of liver cells in ConA model mice by inhibiting Kupffer cells and Fas/FasL system activation.