栀子水提物对雌激素诱导的胆汁淤积大鼠中硫酸化胆酸盐的影响及机制研究  

Effect of Water Extract of Fructus Gardenia on Sulfated Bile Acids in Rats with Estrogen-Induced Cholestasis and Its Mechanism

作　　者：张国强[1] 魏玉辉[1] 文苑洁 饶志[1] 孙文惠 王茜 先柯瑶 武新安[1] ZHANG Guo-qiang;WEI Yu-hui;WEN Yuan-jie;RAO Zhi;SUN Wen-hui;WANG Qian;XIAN Keyao;WU Xin'an(Department of Pharmacy,The First Hospital of Lanzhou University,Lanzhou 730000,China;College of Pharmaceutical Science,Lanzhou University,Lanzhou 730000,China;The First Clinical Medical College of Lanzhou University,Lanzhou 730000,China)

机构地区：[1]兰州大学第一医院药剂科,兰州730000 [2]兰州大学药学院,兰州730000 [3]兰州大学第一临床医学院,兰州730000

出　　处：《中国药学杂志》2020年第20期1680-1685,共6页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金青年基金资助(81702853);国家自然科学基金应急管理项目资助(81641142);国家自然科学基金面上项目资助(81960646,81960680);中华医学会临床药学分会-吴阶平医学基金会科研专项基金资助(320.6750.19090-39);兰州大学创新创业项目医药科学类资助(20190060128)。

摘　　要：目的考察栀子水提物对雌激素诱导的胆汁淤积大鼠肝脏、血液、粪便、尿液中硫酸化胆酸盐的影响及其机制。方法Wistar大鼠随机分为对照组、模型组和栀子组。采用炔雌醇(5 mg·kg^-1)皮下连续注射5 d造肝内胆汁淤积模型,并于造模的同时灌胃给予栀子水提物(120 mg·kg^-1,每天2次)7 d。实验结束后,测定尿液、粪便、血液及肝脏组织中硫酸化胆酸盐含量并考察肝脏及肾脏中Sult2a1、Mrp2和Mrp4的表达量。结果栀子水提物能缓解肝脏病变,增加肝脏、血液、尿液、粪便硫酸化胆酸盐的含量(P<0.05)及肝脏Sult2a1、Mrp2、Mrp4和肾脏Sult2a1、Mrp4的表达(P<0.05)。结论栀子水提物通过调控肝肾Sult2a1、Mrp2和Mrp4的表达,加速胆酸盐的肝脏和肾脏硫酸化转化及排泄,缓解了雌激素诱导的大鼠肝内胆汁淤积。OBJECTIVE To investigate the effects of water extract of Fructus Gardenia on the sulfated bile acids in liver,blood,feces and urine of rats with estrogen-induced cholestasis and its possible mechanism.METHODS Wistar rats were randomly divided into control group,model group and Gardenia group.Intrahepatic cholestasis model was established by subcutaneous injection of ethinylestradiol(5 mg·kg^-1)for 5 d,and the water extract of Gardenia(120 mg·kg^-1,twice a day)was orally administered for 7 d.The levels of sulfated bile acids in urine,feces,blood and liver tissues and the expression of Sult2 a1,Mrp2 and Mrp4 in liver and kidney were determined,respectively.RESULTS Gardenia water extract improved the hepatic lesions,increased the levels of liver,blood,urine and fecal sulfated bile acids(P<0.05)and increased the expression of Sult2 a1,Mrp2 and Mrp4 in liver and the expression of Sult2 a1 and Mrp4 in kidney in EE-treated rats(P<0.05).CONCLUSION Gardenia water extract can accelerate the sulfation transformation and excretion of bile acids in liver and kidney,improve estrogen-induced intrahepatic cholestasis in rats,which may be related to upregulation of the expression of Sult2 a1,Mrp2 and Mrp4 in liver and kidney.

关 键 词：栀子 硫酸化胆酸盐 磺基转移酶2A1 多药耐药相关蛋白2 多药耐药相关蛋白4 

分 类 号：R965[医药卫生—药理学]