雷公藤甲素毒性作用及减毒研究的整合探析

刘斌; 樊丹平; 舒海洋; 何小鹃; 吕诚; 吕爱平

doi:10.13422/j.cnki.syfjx.20191429

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雷公藤甲素毒性作用及减毒研究的整合探析

综述 | 更新时间：2021-02-09

- 雷公藤甲素毒性作用及减毒研究的整合探析
- Side Effect and Attenuation of Triptolide
- 中国实验方剂学杂志 2019年25卷第20期页码：181-190
- 作者机构：
  
  1.中国中医科学院　中医临床基础医学研究所，北京　 100700；
  2.广州中医药大学　第二临床医学院，广州　 510000；
  3.香港浸会大学　中医药学院，香港特别行政区　 999077
- 作者简介：
  
  刘斌，在读硕士，从事中西医结合痹病发病机制研究，E-mail：lynch1123@126.com
  吕爱平，博士，研究员，博士生导师，从事疾病证候分类与中医临床评价方法研究、中药复方作用机制研究及新药研发工作，E-mail：lap64067611@126.com
- 基金信息：
  
  中国中医科学院中央级公益性科研院所基本科研业务费自主选题项目(Z0552;ZZ11-056)
- DOI：10.13422/j.cnki.syfjx.20191429
  中图分类号： R22; R242; R2-031; R285.5;R287
- 收稿日期：2018-12-05，
  
  网络出版日期：2019-04-03，
  
  纸质出版日期：2019-10-20
- 稿件说明：
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刘斌, 樊丹平, 舒海洋, 等. 雷公藤甲素毒性作用及减毒研究的整合探析[J]. 中国实验方剂学杂志, 2019,25(20):181-190.

Bin LIU, Dan-ping FAN, Hai-yang SHU, et al. Side Effect and Attenuation of Triptolide[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 181-190.
刘斌, 樊丹平, 舒海洋, 等. 雷公藤甲素毒性作用及减毒研究的整合探析[J]. 中国实验方剂学杂志, 2019,25(20):181-190. DOI： 10.13422/j.cnki.syfjx.20191429.

Bin LIU, Dan-ping FAN, Hai-yang SHU, et al. Side Effect and Attenuation of Triptolide[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 181-190. DOI： 10.13422/j.cnki.syfjx.20191429.

摘要

雷公藤甲素是从卫矛科植物雷公藤的木质部提取到的环氧二萜内酯类化合物，是雷公藤的主要活性成分之一，具有抗炎、免疫调节及抗肿瘤等生物活性及药理学作用，可以用于治疗类风湿关节炎，多种肿瘤如白血病、乳腺癌、胰腺癌和肺癌等疾病。近年来，雷公藤甲素制剂虽然在临床中得到了一定的应用，但在发挥治疗作用的同时，其对机体消化系统、泌尿系统、生殖系统、循环系统、免疫系统等器官也产生了一些毒性作用，包括肝功能损伤，生育能力下降，胸闷、心悸、心动过缓、房室传导阻滞、心律失常，肾脏功能异常，淋巴器官的萎缩、淋巴组织内淋巴细胞的坏死和细胞数目的减少，免疫功能受损等。这些毒性作用极大限制了雷公藤甲素在临床中的应用，也限制了与其相关的制剂研发，引起了临床医生和科研人员的广泛关注。为了确保雷公藤甲素发挥治疗作用的同时，降低其在使用过程中对机体脏器的毒性，国内外研究者做了大量研究和尝试，如改变雷公藤甲素的化学结构提高其溶解性，开发载药系统削减其毒性，与中草药联合使用增效减毒等。该文对雷公藤甲素在基础研究中产生毒性作用的致毒剂量和机制，以及雷公藤甲素衍生物、载药系统、配伍减毒研究方面进行了整理分析，以期为雷公藤甲素毒性作用及减毒研究的深入探索提供参考。

Abstract

Triptolide (TP) is a kind of epoxy diterpene lactone compound extracted from xylem of

Tripterygium wilfordii

(TWHF). It is one of the main active components of TWHF

with anti-inflammatory

immunomodulatory and anti-tumor activities and pharmacological effect. It can be used in the treatment of rheumatoid arthritis and such cancers as leukemia

breast cancer

pancreatic cancer and lung cancer. In recent years

TP has been gradually applied in clinic and basic research

with a certain curative effect. But it also has certain side effect on digestive system

urinary system

reproductive system

circulatory system and immune system

including liver dysfunction

reduced fertility

chest tightness

heart palpitations

bradycardia

atrioventricular block

arrhythmia

kidney dysfunction

lymphoid organ atrophy

lymphoid tissue necrosis of lymphocytes

and reduction in the number of cells

impaired immune function. These toxic and side effect have greatly restricted the clinical application of TP. In the meantime

the researches and development related to preparations of TP have also been restricted

which has aroused wide attention from clinicians and researchers. To improve the therapeutic effect of TP and reduce the toxicity of TP in the process of application

domestic and foreign researchers have made a lot of studies and attempts

such as changing the chemical structure of TP to improve its solubility

developing drug delivery system to reduce its toxicity and using combination therapy with traditional Chinese herbal medicines to increase efficiency and reduce toxicity. In this paper

the toxic dose and mechanism of TP

TP's derivatives

drug loading system

compatibility and attenuation were integrated to provide ideas for further researches on toxicity and attenuation of TP.

关键词

Keywords

references

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