茵栀黄颗粒对17-α-乙炔雌二醇诱发的肝内胆汁淤积孕大鼠的肝保护作用机制研究  

Protective effect and mechanism of Yinzhihuang Granule on intrahepatic cholestasis of pregnancy induced by 17-α-ethinylestradiol in rats

作　　者：李润 叶晓秀 李贵平 曹晓宽 姚诗晗 董文斌 LI Run;YE Xiao-xiu;LI Gui-ping;CAO Xiao-kuan;YAO Shi-han;DONG Wen-bin(Department of Newborn Medicine,The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Newborn Medicine,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China)

机构地区：[1]西南医科大学附属中医医院新生儿科,四川泸州646000 [2]西南医科大学附属医院新生儿科,四川泸州646000

出　　处：《中国临床药理学杂志》2020年第17期2646-2649,共4页The Chinese Journal of Clinical Pharmacology

基　　金：四川省医学会科研课题基金资助项目(2016ZZ011[GR]);四川省科技厅立项自助基金资助项目(2015JY0209)。

摘　　要：目的研究茵栀黄颗粒(YZH)对雌激素诱发的孕鼠肝内胆汁淤积症(ICP)的保护作用及可能的机制。方法按照体重将妊娠大鼠随机分为4组:正常组、模型组和第1实验组第2实验组,每组10只。大鼠从怀孕的第15天开始,每天四肢后内侧皮下注射17-α-乙炔雌二醇2.5 mL·kg^-1建立ICP大鼠模型。造模的同时,正常组大鼠四肢后内侧皮下注射1,2-丙二醇2.5 mL·kg^-1,第1实验组给予正常大鼠(正常组)灌胃18%茵栀黄颗粒水悬液3.6 g·kg^-1,第2实验组给予模型大鼠(模型组)灌胃18%茵栀黄颗粒水悬液3.6 g·kg^-1,均连续5 d。用化学分析仪测定血清中谷丙转氨酶(GPT)、谷草转氨酶(GOT)和碱性磷酸酶(ALP)活性。用试剂盒法检测胆汁中的总胆汁酸(TBA)水平;以实时定量-PCR技术检测肝中法尼样X受体(FXR)和多耐药相关蛋白2(Mrp2)基因的表达(2-ΔΔCt值)。结果正常组、模型组和第1实验组第2实验组的GPT分别为(48.6±3.7),(114.3±10.2),(40.3±3.9)和(82.0±7.9)U·L^-1;这4组的GOT分别为(60.1±5.8),(156.9±14.3),(62.4±6.0)和(89.7±9.1)U·L^-1;这4组的ALP分别为(62.4±6.4),(289.2±20.3),(72.1±6.2)和(178.3±19.1)U·L^-1;这4组的TBA分别为(1429.1±130.4),(5109.8±489.2),(1388.7±142.3)和(1213.1±130.6)μmol·L^-1;这4组的FXR基因表达分别为100.2±9.9,301.4±28.2,89.7±9.7和124.0±13.1;这4组的Mrp2基因表达分别为100.0±9.8,289.1±27.4,102.3±10.1和120.9±13.1。上述指标:模型组与正常组比较,差异均有统计学意义(均P<0.01);第2实验组与模型组比较,差异均有统计学意义(P<0.05,P<0.01)。结论茵栀黄介导的对胆汁淤积性肝损伤的保护作用可能依赖于调控FXR和Mrp2的表达。Objective To study the protective effect of Yinzhihuang Granule(YZH)on intrahepatic cholestasis of pregnancy(ICP)of estrogen-induced in pregnant rats and explore its possible mechanism.Methods SD rats pregnant were randomly divided into 4 groups according to weight:normal group,model group,experimental-1,-2 groups,with 10 rats in each group.Rats from 15 th day of pregnancy,ICP rat model was established through daily subcutaneous injection of 17α-ethinylestradiol 2.5 mL·kg^-1.At the same time of molding,subcutaneous injection of 1,2-propanediol 2.5 mL·kg^-1 into the hind medial side of the limbs of rats in normal group;the experimental-1 group was given 18%Yinzhihuang Granule water suspension 3.6 g·kg^-1 by gavage to normal rats(normal group);the experimental-2 group was given 18%Yinzhihuang Granule water suspension 3.6 g·kg^-1 by gavage to model rats(model group),for 5 d.The activity of the glutamic-pyruvic transaminase(GPT),glutamic-oxaloacetic transaminase(GOT),alkaline phosphatase(ALP),andγ-glutamyl transpeptidase(γ-GT)were measured by Chemical analyzer.The level of the total bile acids(TBA)in bile was detected by kit.The expression(2-ΔΔCtvalue)of farnesoid X receptor(FXR)and multidrug resistance-associated protein 2(Mrp2)mRNA in liver was detected by real-time quantitative-PCR.Results GPT in normal group,model group,experimental-1,-2 groups were respectively(48.6±3.7),(114.3±10.2),(40.3±3.9),(82.0±7.9)U·L^-1;GOT in the 4 groups were respectively(60.1±5.8),(156.9±14.3),(62.4±6.0),(89.7±9.1)U·L^-1;ALP in the 4 groups were respectively(62.4±6.4),(289.2±20.3),(72.1±6.2),(178.3±19.1)U·L^-1;TBA in the 4 groups were respectively(1429.1±130.4),(5109.8±489.2),(1388.7±142.3),(1213.1±130.6)μmol·L^-1;expression of FXR mRNA in the 4 groups were respectively 100.2±9.9,301.4±28.2,89.7±9.7,124.0±13.1;expression of Mrp2 mRNA in the 4 groups were respectively 100.0±9.8,289.1±27.4,102.3±10.1,120.9±13.1.Comparison between model group and normal group,the difference of the factors were signif

关 键 词：茵栀黄颗粒 17-α-乙炔雌二醇 孕鼠肝内胆汁淤积症 类法尼醇X核内受体 多耐药相关蛋白2 

分 类 号：R28[医药卫生—中药学]