中国药物警戒 ›› 2018, Vol. 15 ›› Issue (9): 513-517.

• 基础与临床研究 •    下一篇

何首乌4种单体成分灌胃14天的小鼠肝肾毒性研究

宋蕾1,2, 王琴1, 毕亚男1, 史红1,2, 张玥1,2, 周昆1,2*   

  1. 1天津中医药大学中医药研究院,天津 300193;
    2天津市中药药理学重点实验室,天津 300193
  • 收稿日期:2018-11-02 修回日期:2018-11-02 出版日期:2018-09-20 发布日期:2018-11-02
  • 通讯作者: 周昆,男,硕士,副研究员,硕士生导师,中药药理毒理研究。E-mail:z.k.ken@263.net
  • 作者简介:宋蕾,女,硕士,助理实验师,中药药理毒理研究。

Study on Liver and Kidney Toxicity of 4 Components of Polygoni Multifori Radix on Mice after Intragastric Administration for 14 Days

SONG Lei1,2, WANG Qin1, BI Yanan1, SHI Hong1,2, ZHANG Yue1,2, ZHOU Kun1,2*   

  1. 1Medicine Research Institute, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China;
    2Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin 300193, China
  • Received:2018-11-02 Revised:2018-11-02 Online:2018-09-20 Published:2018-11-02

摘要: 目的 研究何首乌中的4种单体成分二苯乙烯苷、大黄酸、大黄素甲醚、大黄素的肝肾毒性,为何首乌的肝毒性研究提供有益探索。方法 50只ICR小鼠随机分为对照组、二苯乙烯苷组、大黄酸组、大黄素甲醚组和大黄素组。每组按照100 mg·kg-1剂量灌胃给药,每天给药1次,对照组给予相应量的生理盐水,连续给药14 d。末次给药结束后,各组小鼠禁食不禁水12 h,称重,取血并剖取肝脏、肾脏,计算肝系数和肾系数,检测血清生化指标和肝脏胆汁酸转运体mRNA变化。结果 大黄酸、大黄素甲醚和大黄素组小鼠体重显著降低(P <0.05),大黄酸给药组小鼠的肝系数显著升高(P <0.05);二苯乙烯苷可同时显著升高TG、CRE、ALB和GLU的水平(P <0.05或P <0.01),蒽醌类成分大黄素、大黄酸、大黄素甲醚均可引起BUN显著降低(P <0.05或P <0.01),大黄酸和大黄素均可引起TG显著下降(P <0.05或P <0.01);4种单体成分对胆汁酸转运体MRP2、BSEP等作用显著(P <0.05或P <0.01)。结论 何首乌的4种单体成分二苯乙烯苷、大黄酸、大黄素甲醚、大黄素按照100 mg·kg-1 剂量灌胃给药14 d可改变ICR小鼠的血清生化指标,对不同胆汁酸转运体有明显的作用。

关键词: 何首乌, 肝损伤, 小鼠, 胆汁淤积, 胆汁酸转运体

Abstract: Objective To study the liver and kidney toxicity of stilbeneglycoside, rhein, physcion and emodin and provide useful exploration for the hepatotoxicity study of Polygoni Multifori Radix. Methods 50 ICR mice were randomly divided into control group, stilbeneglycoside group, rhein group, physcion group and emodin group. Intragastric administration was performed once daily with the dosage of 100 mg·kg-1 and the control group was given a corresponding amount of normal saline for 14 days. After the last delivery, foods were forbidden but the water was provided for 12 hours. The body weights were weighed and serum, liver and kidney were obtained to calculate the hepatic index and renal coefficient. Serum biochemical indicators and mRNA level of liver bile acid transporter were detected. Results The body weight of rhein, physcion and emodin groups were lower than the control group (P <0.05) and the hepatic index of rhein increased significantly (P <0.05). TG, CRE, ALB and GLU of stilbeneglycoside group increased markedly (P <0.05 or P <0.01). Rhein, physcion and emodin of anthraquinones made BUN dramatically decreased (P <0.05 or P <0.01), while rhein and emodin could induce TG decreased (P <0.05 or P <0.01). The 4 drugs had significant effects on bile acid transporters such as MRP2 and BSEP (P <0.05 or P <0.01). Conclusion Stilbeneglycoside, rhein, physcion and emodin of Polygoni Multifori Radix could change the serum biochemical indicators of ICR mice with the dosage of 100 mg·kg-1 for 14 days and have obvious effects on different bile acid transporters.

Key words: Polygoni Multifori Radix, liver injury, mice, cholestasis, bile acid transporter

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