苷泰胶囊对GalN/LPS致小鼠急性肝损伤的保护作用研究  

Protective Effect of Gantai Capsules on GalN/LPS-induced Acute Liver Injury in Mice

作　　者：李光全[1,2] 崔鹤蓉[2] 刘慧敏[2] 张振芳[2] 孟雅坤 桑秀秀 柏兆方[2] 王家葵[1] 

机构地区：[1]成都中医药大学药学院,四川成都611137 [2]中国人民解放军第三0二医院,北京100039

出　　处：《亚太传统医药》2016年第10期5-8,共4页Asia-Pacific Traditional Medicine

基　　金：国家自然科学基金资助项目(81330090,81503350)

摘　　要：目的:研究观察苷泰胶囊对D-氨基半乳糖(GalN)联合细菌脂多糖(LPS)诱导的小鼠急性肝脏损伤的保护作用,并探讨其作用机制。方法:将60只Balb/c小鼠随机分为正常组、模型组、双环醇阳性药对照组(10mg·kg^(-1))和苷泰胶囊低、高剂量(300、3000mg·kg^(-1))组,每组12只。除正常组、模型组给予等体积生理盐水外,各组小鼠均按给定药物、剂量灌胃7日,每日1次。末次给药1h后,正常组小鼠腹腔注射等容积生理盐水,其他各组均腹腔注射GalN(800mg·kg^(-1))和LPS(10μg·kg^(-1))。给药4h后取血取肝。通过血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)的含量和HE染色结果评价苷泰胶囊对肝损伤的保护效果。采用Real-time PCR检测各组小鼠肝组织TNF-α、IFN-γ、CD14和TLR4等基因的表达。结果:苷泰胶囊可明显降低急性肝损伤小鼠的ALT、AST水平(P<0.05或P<0.01),改善其肝脏病理损伤程度,同时下调TNF-α、IFN-γ、CD14和TLR4等基因的表达(P<0.05或P<0.01)。结论:苷泰胶囊对GalN/LPS诱导的急性肝损伤小鼠具有较好的保护作用,其机制可能与下调LPS受体CD14、TLR4mRNA表达,抑制TLR4信号通路的活性,进而抑制TNF-α、IFN-γ等炎症因子的表达有关。Objective：To investigate the protective effects of Gantai Capsules（GTC）on GalN/LPS-induced acute liver injury in mice,and explore its mechanism.Methods：Experimental Bal/c mice were randomly divided to the normal group,model group,the positive control group（Colchicine,2mg·kg（-1））,and the GTC groups（300,3 000mg·kg（-1））,12 mice in each group.The mice in normal and model groups were administrated with an equal volume of saline,while the other groups were received gavage with corresponding substances at a given dose once a day,for 7days.After that,the mice in normal group were administrated with an equal volume of saline,while the other mice for acute liver injury were established by intraperitoneal injection of D-galactosamine（GalN,800mg·kg（-1））combined with lipopolysaccharide（LPS,10μg·kg（-1））just for once.The protective effects of GTC on acute liver injury were evaluated by the activities of serum alanine transaminase（ALT）and aspartate transaminase（AST）,and the pathologic changes in liver tissues were observed by HE staining.In addition,the mRNA expression levels of TNF-α,IFN-γ,CD14 and TLR4in liver tissues were measured by Real-time PCR.Results：GTC obviously decreased activities of serum ALT and AST in GalN/LPS-induced acute liver injury induced in mice（P〈0.05 or P〈0.01）,and significantly reduced the hepatic cell degeneration and necrosis in HE staining result.The results of Real-time PCR revealed that GTC suppressed the mRNA expression of TNF-α,IFN-γ,CD14 and TLR4（P〈0.05 or P〈0.01）.Conclusion：GTC could alleviate acute liver injury induced by GalN/LPS in mice.Its probable mechanisms may be associated with the down-regulation of the mRNA expressions of CD14 and TLR4,then,inhibit the activity of TLR4 signal pathway,thereby inhibiting the releases of proinflammatory cytokines,such as TNF-αand IFN-γ.

关 键 词：急性肝损伤 苷泰胶囊 保护作用 实验研究 

分 类 号：R285.5[医药卫生—中药学]