| 何首乌水提物大鼠连续灌胃给药28 d肝毒性研究——胆汁淤积相关机制探讨 |
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| 引用本文： | 王涛,王佳颖,周植星,江振洲,李妍妍,张良,张陆勇.何首乌水提物大鼠连续灌胃给药28 d肝毒性研究——胆汁淤积相关机制探讨[J].中国中药杂志,2015,40(11):2163-2167. |
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| 作者姓名： | 王涛 王佳颖 周植星 江振洲 李妍妍 张良 张陆勇 |
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| 作者单位： | 中国药科大学 江苏省新药筛选中心, 江苏 南京 210009,南京中医药大学 药物安全性评价中心, 江苏 南京 210023,天津药物研究院 天津市新药设计与发现重点实验室, 天津 300193,中国药科大学 江苏省新药筛选中心, 江苏 南京 210009,中国药科大学 江苏省新药筛选中心, 江苏 南京 210009,南京中医药大学 药物安全性评价中心, 江苏 南京 210023,中国药科大学 江苏省新药筛选中心, 江苏 南京 210009 |
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| 基金项目： | 国家自然科学基金重大国际(地区)合作研究项目(81320108029);江苏省中药药效与安全性评价重点实验室开放课题 |
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| 摘 要： | 目的:考察何首乌水提物(AEPM)对大鼠肝脏中胆汁酸合成、代谢、转运相关分子影响,探讨何首乌肝毒性相关机制。 方法:SD大鼠分别灌胃AEPM 60,30 g·kg-1,每天1次,连续28 d。28 d后解剖取肝脏,分别采用荧光定量PCR和Western blot检测肝脏MRP3,MRP2,BSEP,FXR,CYP7A1等分子的mRNA和蛋白表达水平。 结果:与正常组相比,AEPM高剂量组雄性大鼠肝脏中MRP3和BSEP的mRNA表达均显著升高(P<0.05),而AEPM高、低剂量组肝脏FXR的mRNA表达均显著降低(P<0.05);AEPM高、低剂量组雌性大鼠肝脏 MRP3,MRP2,BSEP,CYP7A1的mRNA表达均显著升高(P<0.05)。Western blot检测结果显示,AEPM高、低剂量给药组雄性和雌性大鼠肝脏中MRP3,MRP2,BSEP,FXR,CYP7A1蛋白表达水平与mRNA变化基本一致,但均未达统计学显著差异。 结论:AEPM大鼠灌胃给药28 d对肝脏胆汁酸合成、转运、排泄相关蛋白的表达具有一定的影响,在mRNA表达水平既具有胆汁淤积分子特征,同时也可见促进胆汁酸排泄的分子特征。
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| 关 键 词： | 何首乌水提物 大鼠 肝毒性 胆汁酸转运体 法尼酯衍生物X受体 |
| 收稿时间： | 2014/9/30 0:00:00 |
Study on hepatotoxicity of aqueous extracts of Polygonum multiflorum in rats after 28-day oral administration: cholestasis-related mechanism |
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| WANG Tao,WANG Jia-ying,ZHOU Zhi-xing,JIANG Zhen-zhou,LI Yan-yan,ZHANG Liang and ZHANG Lu-yong.Study on hepatotoxicity of aqueous extracts of Polygonum multiflorum in rats after 28-day oral administration: cholestasis-related mechanism[J].China Journal of Chinese Materia Medica,2015,40(11):2163-2167. |
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| Authors: | WANG Tao WANG Jia-ying ZHOU Zhi-xing JIANG Zhen-zhou LI Yan-yan ZHANG Liang and ZHANG Lu-yong |
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| Institution: | Jiangsu Center of New Drug Screening, China Pharmaceutical University, Nanjing 210009, China,Drug Safety Evaluation Center, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China,Tianjin Key Laboratory of New Drug Design and Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China,Jiangsu Center of New Drug Screening, China Pharmaceutical University, Nanjing 210009, China,Jiangsu Center of New Drug Screening, China Pharmaceutical University, Nanjing 210009, China,Drug Safety Evaluation Center, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China and Jiangsu Center of New Drug Screening, China Pharmaceutical University, Nanjing 210009, China |
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| Abstract: | Objective: To study the effect of aqueous extracts of Polygonum multiflorum (AEPM) on bile acid synthesis, metabolism and transfer-related molecules in rat liver and the hepatotoxicity-related mechanism of P. multiflorum. Method: Sprague-Dawley rats were orally administered with 30, 60 g·kg-1 APEM once everyday for consecutively 28 days. At the end of the experiment, mRNA and protein expressions of hepatic MRP3, MRP2, BSEP, FXR and CYP7A1 were detected by Real-time PCR and Western blot. Result: Compared with the normal group, the AEPM high dose group showed significant increases in mRNA expressions of hepatic MRP3 and BSEP of male rats (P<0.05); AEPM high and low dose groups revealed a notable decrease in mRNA expressions of hepatic FXR (P<0.05) and remarkable rises in mRNA expressions of hepatic MRP3, MRP2, BSEP, CYP7A1 among female rats (P<0.05). According to the test results of western blot assay, AEPM high and low dose groups showed consistent changes in protein and mRNA expressions hepatic MRP3, MRP2, BSEP, FXR, CYP7A1. Conclusion: The 28 oral administration with AEPM in rats showed a certain effect on expressions of bile acid synthesis, metabolism and transfer-related proteins, as well as cholestatic or choleretic effects in the mRNA expression. |
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| Keywords: | aqueous extracts of Polygonum multiflorum rat hepatotoxicity bile acid transporter Farnesoid X receptor |
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