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[近20年雷公藤肝毒性研究概述]

[Overview of hepatotoxicity studies on Tripterygium wilfordii in recent 20 years].

作者信息

Tian Ya-Ge, Su Xiao-Hui, Liu Li-Ling, Kong Xiang-Ying, Lin Na

机构信息

Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences Beijing 100700,China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2019 Aug;44(16):3399-3405. doi: 10.19540/j.cnki.cjcmm.20190527.408.

Abstract

Tripterygium wilfordii is widely used in the treatment of rheumatism with curative effect. However,its toxicity and adverse reactions,especially the hepatotoxicity,rank the first in the herbs induced liver injury,is the key factors hindering its clinical application. This paper reviewed the literatures related to the hepatotoxicity of T. wilfordii in recent 20 years,and summarized the characteristic of hepatotoxicity induced by T. wilfordii,the factors causing liver injury,the mechanism of toxicity,and the measures to reduce toxicity. In animal experiments,the T. wilfordii induced-hepatotoxicity in physiological state was more serious than pathological state. The T. wilfordii induced-hepatotoxicity is related to various toxic components contained in it,but alkaloids are the most toxic one.Overdose and cumulative overdose are the lead causing of hepatotoxicity induced by T. wilfordii. The theory of oxidative stress is still an important mechanism of T. wilfordii induced-hepatotoxicity,and Nrf2,as a key regulatory enzyme of oxidative stress,has become an important target for drugs to against T. wilfordii induced-hepatotoxicity. Mitochondrial autophagy and liver hypersensitivity are new mechanisms of liver injury induced by T. wilfordii. The measures such as dosage control,drug compatibility and dosage form variations can help to reduce the hepatotoxicity induced by T. wilfordii. This paper clarified the current situation and shortcomings of safety research on T. wilfordii,so as to propose new research strategies and provide ideas for rational evaluation of safety and clinical safe drug use of T. wilfordii.

摘要

雷公藤广泛用于治疗风湿病且疗效显著。然而,其毒性和不良反应,尤其是肝毒性,在草药引起的肝损伤中位居首位,是阻碍其临床应用的关键因素。本文综述了近20年雷公藤肝毒性的相关文献,总结了雷公藤所致肝毒性的特点、肝损伤的影响因素、毒性机制以及减毒措施。在动物实验中,生理状态下雷公藤所致肝毒性比病理状态下更严重。雷公藤所致肝毒性与其所含多种毒性成分有关,但生物碱毒性最强。过量及累积过量是雷公藤致肝毒性的主要原因。氧化应激理论仍是雷公藤致肝毒性的重要机制,而Nrf2作为氧化应激的关键调节酶,已成为抗雷公藤致肝毒性药物的重要靶点。线粒体自噬和肝脏超敏反应是雷公藤致肝损伤的新机制。控制剂量、药物配伍及剂型改变等措施有助于减轻雷公藤所致肝毒性。本文阐明了雷公藤安全性研究的现状与不足,以期提出新的研究策略,为合理评价雷公藤的安全性及临床安全用药提供思路。

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