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。
Abstract
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 Sult2a1, 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 Sult2a1, Mrp2 and Mrp4 in liver and the expression of Sult2a1 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 Sult2a1, 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
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Key words
Fructus Gardenia /
sulfated bile acids /
Sult2a1 /
Mrp2 /
Mrp4
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中图分类号：
R965
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参考文献
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脚注
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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)
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