高脂乳剂复合肝损伤药物诱导非酒精性脂肪性肝炎小鼠模型的研究  

Study on an animal model of nonalcoholic steatohepatitis induced by high-fat emulsion combined with liver injury drugs

作　　者：谭婉莹 王淳[1,2] 杜仕静 熊静悦 扈晓宇[1] 谭正怀[2] TAN Wanying;WANG Chun;DU Shijing;XIONG Jingyue;HU Xiaoyu;TAN Zhenghuai(Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan,610075 P.R.China;Sichuan Provincial Key Laboratory of Quality and Innovation Research of Chinese Materia Medica,Sichuan Academy of Chinese Medicine Sciences,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]成都中医药大学,四川成都610075 [2]四川省中医药科学院中药材品质及创新中药研究四川省重点实验室,四川成都610041

出　　处：《华西药学杂志》2024年第2期151-155,共5页West China Journal of Pharmaceutical Sciences

基　　金：四川省科技厅中央引导地方发展专项(2021ZYD0088)。

摘　　要：目的建立复合型非酒精性脂肪性肝炎(NASH)动物模型,进一步揭示NASH的发病机制,为防治NASH新药疗效评价提供理想工具。方法采用三因素二水平正交设计,小鼠分别给予地塞米松(Dex)、四环素(Tet)、高脂乳剂(HF)及联合用药7 d后,测定小鼠血清肝功、血脂生化指标水平,肝脏脂质水平,并对肝脏进行病理组织学分析。结果Dex、Tet单独使用均能引起肝功、血脂及肝脏脂质水平明显异常,而HF单独使用对肝功的影响甚小。析因分析结果显示:Dex是引起多个指标异常的关键因素,包括丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBiL)、直接胆红素(DBiL)、血脂及肝脏脂质。而Tet仅对部分指标有作用,包括转氨酶及胆红素。HF主要影响血清及肝脏内胆固醇水平。Dex与HF联用在升高血清及肝脏总胆固醇(TC)水平上具有明显的协同增效作用;引起肝脏甘油三酯(TG)升高的主要因素是Dex,当与Tet及HF联用时,可产生显著的协同增效作用。结论Dex与HF联用可在较短时间内形成较理想的NASH小鼠模型,是较简便的、可用于防治NASH药物筛选的较好动物模型。OBJECTIVE To establish an animal model of compound nonalcoholic steatohepatitis(NASH),to further reveal the pathogenesis of NASH and to provide an ideal tool for evaluating the efficacy of new drugs for prevent and treat NASH.METHODS Three factor two level orthogonal design was used.After 5 days of dexamethasone,tetracycline,high-fat emulsion and combination of dexamethasone and tetracycline administration,serum liver function,blood lipid and other biochemical indexes,liver lipid level were measured,and liver histopathology was analyzed.RESULTS Dexamethasone and tetracycline alone could cause significant abnormalities in liver function level,blood lipid level and liver lipid level,while high-fat emulsion alone had lttle effect on liver function.The results of factorial analysis showed that dexamethasone was the key factor causing the abnormality of multiple indicators,including ALT,AST,TBiL,DBiL,blood lipid and liver lipid.Tetracycline only affects some indexes,including transaminase and bilirubin.High fat emulsion mainly affected the cholesterol level in serum and liver.The combination of dexamethasone and high fat emulsion had obvious synergistic effect on increasing serum and liver TC levels.The main factor causing the increase of liver TG was dexamethasone.When combined with tetracycline and HF,it could produce a significant synergistic effect.CONCLUSION Both dexamethasone and liver injury drugs or high-fat emulsion have significant synergistic effect,suggesting that the formation of NASH is related to endocrine,liver function and blood lipid level.The combination of dexamethasone and high-fat emulsion can form a relatively ideal NASH mouse model in a relatively short time,which is a relatively simple and good animal model for screening drugs to prevent and control NASH.

关 键 词：正交设计 非酒精性脂肪性肝炎 地塞米松 四环素 高脂乳剂 动物模型 

分 类 号：R96[医药卫生—药理学]