吴茱萸水煎液致小鼠肝毒性机制研究  

Mechanism of Liver Toxicity Induced by Euodiae Fructus Decoction in Mice

作　　者：周璐[1] 姚广涛[1] 曹智丽[1] 徐婷婷[1] 金若敏[1] 

机构地区：[1]上海中医药大学药物安全评价研究中心,上海201203

出　　处：《中国实验方剂学杂志》2013年第22期269-272,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家科技重大专项项目(2009ZX09502-002);国家重点基础研究发展计划(973计划)项目(2009CB522807);国家科技重大专项课题(2011ZX09301-009)

摘　　要：目的:探讨吴茱萸致小鼠肝脏损害的毒性机制。方法:昆明种小鼠随机分为吴茱萸高剂量组(30 g·kg-1·d-1)、中剂量组(20 g·kg-1·d-1)、低剂量组(10 g·kg-1·d-1)和正常组,连续灌胃给药或蒸馏水21 d后,摘眼球取血,离心,取血清检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)。取肝脏,计算脏器指数并观察肝组织形态学改变。测定肝组织中超氧化物歧化物(SOD)活性、丙二醛(MDA)含量、谷胱甘肽脱氢酶(GSH)含量、谷胱甘肽过氧化物酶(GSH-Px)活性、一氧化氮合酶(NOS)活性,计算SOD/MDA;采用ELISA法测定肝组织中炎症介质肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)水平。结果:与正常组比较,吴茱萸3个剂量组小鼠血清ALT,AST明显升高,肝脏肝组织形态学出现肝细胞灶性坏死。肝组织中SOD/MDA,GSH-Px和NOS活性明显下降(P<0.05),GSH含量显著升高(P<0.05);炎症介质TNF-α,IL-1β,IL-6含量显著升高(P<0.01)。结论:大剂量吴茱萸致小鼠肝毒性的机制可能与自由基及炎症因子的产生有关。Objective：To explore mechanism of the liver injury caused by giving Eudiae Fructus evodiae decoction in mice.Method：KM mice were divided into four groups：normal control,high,middle and low dose groups which were administrated respectively with distilled water or equal volume of Euodiae Fructus decoction at the doses of crude drug 30,20,10 g ·kg-1 daily by gavage for consecutive 21 days.The blood of the animals was collected by pulling out the eyeball.The activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined by automatic biochemical analyzer.The livers were collected.The liver weight indexes were calculated and liver pathological changes were observed.The activity of superoxide dismutase （SOD）,glutathione （GSH）,glutathione peroxidase （GSH-Px）,nitric oxide synthase （NOS） and the contents of malonaldehyde （MDA） in liver samples were measured by Kit.The ratio of SOD/MDA was calculated.The contents of interleukin-1β （IL-1β）,interleukin-6 （IL-6）,tumor necrosis factor-α （TNF-α） in liver samples were detected by ELISA.Result：Compared with control group,the activities of ALT and AST were significantly increased in high,middle and low dose groups.The liver histopathological change was characterized by emergence of focal necrosis of liver cells.The activity of GSH-Px,NOS and the ratio of SOD/MDA in the liver were significantly decreased （P 〈 0.05）,the tissue content of GSH was increased （P 〈 0.05）,the contents of IL-1β,IL-6,TNF-α of the liver were significantly increased （P 〈0.01）.Conclusion：The mechanism of the liver injury caused by high dose of Euodiae Fructus decoction in mice may be related to oxidative stress and inflammatory response.

关 键 词：吴茱萸 肝毒性机制 自由基 炎症因子 

分 类 号：R285.5[医药卫生—中药学]