甘草水煎液对α-萘异硫氰酸酯诱导的肝内胆汁淤积性损伤的防治及其机理研究  

Preventive treatment effect and its mechanism of Liquorice Decoction against ANIT-induced cholestatic liver injury in mice

作　　者：沈淑娇[1] 张志荣[1] 张林林[1] 樊玉娟[1] 谭波[1] 李玥[1] 蒋健[1] 裘福荣[1] 

机构地区：[1]上海中医药大学附属曙光医院,临床药代动力学实验室,上海201203

出　　处：《中国临床药理学与治疗学》2016年第12期1321-1327,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(81173118);上海市中医临床重点实验室项目(C10d Z2220200)

摘　　要：目的:探讨甘草水煎液对α-萘异硫氰酸酯(ANIT)所致肝内胆汁淤积症(IC)模型小鼠肝损伤的防治作用。方法:雌性C57BL/6小鼠随机分为正常组、模型组、甘草低剂量组(1.13 g·kg^(-1)·d^(-1))、甘草中剂量组(2.25 g·kg^(-1)·d^(-1))及甘草高剂量组(4.50 g·kg^(-1)·d^(-1)),连续给药10 d,检测总胆红素(TBIL)、谷丙转氨酶(ALT)、谷草转氨酶(AST)及碱性磷酸酶(ALP)水平,HE染色观察肝脏病理,用LC-MS/MS测定血浆胆汁酸含量,RT-PCR检测孕烷受体、细胞色素P450 3A11、尿苷二磷酸葡萄糖醛酸转移酶1A1和胆酸盐外排泵。结果:与模型组相比,甘草低、中剂量组ALT、AST和ALP有下降趋势;甘草高剂量组ALT、AST和ALP水平明显降低(P<0.05);与模型组比较,血浆CA浓度在甘草低、中、高剂量分别减少32.2%、55.1%和84.4%;血浆CDCA浓度在高剂量减少45.8%;血浆DCA浓度在甘草低、中、高剂量分别减少49.1%、52.5%和67.1%;血浆LCA浓度在甘草低、中、高剂量分别减少59.5%、59.5%和56.7%。甘草水煎液可增加孕烷受体、细胞色素P450 3A11、尿苷二磷酸葡萄糖醛酸转移酶1A1和胆酸盐外排泵的mRNA转录(P<0.05),并呈剂量依赖性。结论:甘草水煎液可促进胆汁酸代谢和排泌,减轻胆汁酸负荷,对IC肝损伤起防治作用。AIM： To investigate the liver protection and mechanism of Liquorice Decoction on IC model mice induced by ANIT. METHODS： Female C57 BL /6 mice were randomly divided into normal group,model group,low-dose treatment group（ 1. 13 g·kg^-1·d^-1）,middle-dose treatment group（ 2. 25 g·kg^-1·d^-1） and high-dose treatment group（ 4. 50 g·kg^-1·d^-1）. The C57BL/6 mice were administrated with Liquorice Decoction for 10 days except for the normal group. Then,TBIL,ALT,AST and ALP levels were detected. Hepatic pathological changes were observed by HE staining. The plasma bile acid was determined by LC-MS / MS. PXR,CYP3A11,UGT1A1 and BSRP were quantized by RT-PCR. RESULTS： Compared with the model group,the levels of ALT,AST and ALP in liquorice low-dose and middle-dose group had a downward trend; while in liquorice high-dose group, ALT,AST and ALP levels showed significant decrement（ P〈0. 05）. Compared with the model group,concentration of CA in plasma was decreased by 32.2%,55. 1% and 84. 4% in liquorice low-,middleand high-dose group,respectively. Concentration of CDCA in plasma was decreased by 45. 8% in highdose group. Concentration of DCA in plasma was decreased by 49. 1%,52. 5% and 67. 1% in liquorice low-,middle- and high-dose group,respectively. Moreover,concentration of LCA in plasma was decreased by 59. 5%,59. 5% and 56. 7% in liquorice low-,middle- and high-dose group,respectively. Liquorice decoction could elevate the transcription of mRNA for PXR,CYP3A11,UGT1A1,and BSEP（ P〈0. 05） with dose-dependent models.CONCLUSION： Liquorice Decoction could improve liver necrosis and liver function,and had a certain protective effect on the liver damage of IC mice.

关 键 词：甘草水煎液 肝内胆汁淤积症 孕烷受体 防治机制 

分 类 号：R965.2[医药卫生—药理学]