苦参碱预防大鼠胆汁淤积性肝损伤作用机制的研究  

Matrine prevents cholestatic liver injury in rats

作　　者：阳丽梅[1] 黄旭慧[1,2] 张倩文 陈淑芳 YANG Limei;HUANG Xuhui;ZHANG Qianwen;CHEN Shu-fang(Department of Pharmacy,Fujian Provincial Hospital,Provincial Clinical Medical College of Fujian Medical University,Fuzhou,Fujian 350001,China)

机构地区：[1]福建医科大学省立临床医学院,福建省立医院药学部,福州350001 [2]福建省立金山医院药学部 [3]福建医科大学药学院

出　　处：《福建医药杂志》2019年第5期8-12,共5页Fujian Medical Journal

基　　金：福建省医学创新课题(2016-CX-15)

摘　　要：目的探讨苦参碱(MT)预防胆汁淤积性肝损伤的作用机制。方法将大鼠随机分成生理盐水(NS)组、ANIT模型组、熊去氧胆酸(UDCA)组、MT低剂量组(5 mg/kg)和MT高剂量组(10 mg/kg),采用α-萘异硫氢酸酯(ANIT)(60 mg/kg)建立胆汁淤积性肝损伤模型,连续灌胃给药7天,实验结束前禁食24 h,不禁水,然后采血、取肝脏。全自动生化仪测定丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、血清总胆红素(TBiL)和碱性磷酸酶(ALP)水平,逆转录-聚合酶链反应(RT-PCR)法检测大鼠肝脏中CYP7A1和FXR mRNA表达,蛋白质免疫印记(WB)法检测大鼠肝脏中胆酸合成基因CYP7A1和FXR蛋白的表达。结果与ANIT模型组相比,MT低、高剂量组ALT、AST、TBiL和ALP均明显降低(P<0.01)。与ANIT模型组比较,UDCA组、MT低剂量组和MT高剂量组的FXR mRNA表达分别上调31%(P=0.059)、78%(P=0.001)、39%(P=0.05),CYP7A1 mRNA表达分别上调69%(P=0.102)、257%(P=0.005)和143%(P=0.024)。在蛋白表达水平,与ANIT模型组比较,UDCA组、MT低剂量组、MT高剂量组的FXR蛋白表达分别上调23%(P=0.065)、55%(P=0.005 6)和46%(P=0.035),而CYP7A1的蛋白表达分别下调34%(P=0.105)、42%(P=0.007 1)和5%(P=0.205)。结论苦参碱预防大鼠胆汁淤积性肝损伤,可能通过调控FXR、CYPA7A1的基因及蛋白表达来实现。Objective To determine the mechanism of matrine(MT)in preventing cholestatic liver injury.Methods a-naphthalene isothionate(ANIT)(60 mg/kg)was used to establish the cholestatic liver injury model in SD rats.All rats were randomly divided into four groups,which were normal saline(NS)group,ANIT model group,UDCA group,low-dose MT(5 mg/kg)group and high-dose MT(10 mg/kg)group.All rats were administered ANIT orally for seven days,fasting 24 h before the end,and their blood and livers were collected in the end.Automatic biochemical analyzer was used for detection of liver function indicators alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBiL)and alkaline phosphatase(ALP).RT PCR was used to detect the mRNA expression of cholesterol synthesis 7cx-hydroxylase(CYP7A1)and far nesoid receptor(FXR)in rat liver,and Western blot(WB)was used to detect the expression of CYP7Al and FXR protein.Results Compared with ANIT model group,low-dose and high-dose MT decreased ALT,AST,TBiL and ALP significantly.FXR mRNA expression of UDCA,low-dose MT and high-dose MT groups increased by 31%(P=0.059),78%(P=0.001)and 39%(P=0.05)than ANIT model group,while the CYP7A1 mRNA expression of these three groups increased by 69%(P=0.102),257%(P=0.005)and 143%(P=0.024)than ANIT model group,respectively.FXR protein expression of UDCA,low-dose MT and high-dose MT groups increased by 23%(P=0.006 5),55%(P=0.005 6)and 46%(P=0.035)than ANIT model group,while the CYP7Al protein expression of these three groups decreased by 34%(P=0.105),42%(P=0.007 1)and 5%(P=0.205)than ANIT model group,respectively.Conclusion MT could improve cholestatic liver injury in rats,the mechanism of which might be related to regulate the expression of FXR and CYP7 Al gene and protein.

关 键 词：苦参碱 胆汁淤积性肝损伤 胆固醇7Α-羟化酶 法尼醇受体 

分 类 号：R332[医药卫生—人体生理学] R575[医药卫生—基础医学]