雷公藤甲素生殖毒性及其防治策略研究进展

Research progress in reproductive toxicity of triptolide and ways of mitigation

雷公藤甲素是传统中药雷公藤中最主要的生物活性成分,具有抗癌、抗炎和免疫抑制等功效,临床上用于治疗肿瘤,类风湿性关节炎和系统性红斑狼疮等自身免疫疾病。然而,雷公藤甲素具有严重的生殖毒性,会造成精子数量减少和活力下降,直接损伤睾丸、卵巢和子宫等,其毒性机制主要与氧化应激、线粒体损伤,及乳腺癌耐药蛋白、过氧化物酶体增殖物激活受体和半胱氨酸蛋白酶3等蛋白表达异常及支持细胞、间质细胞、生精上皮细胞、线粒体和溶酶体等中的标志酶活力下降相关。可通过雷公藤甲素毒性缓解药物、化学结构修饰和新型递药系统等方式缓解雷公藤甲素的生殖毒性。本文主要对雷公藤甲素的生殖毒性、毒性机制及缓解措施的最新研究进展进行综述,为其临床合理应用提供依据。

Triptolide is the most important biologically active ingredient of the traditional Chinese medicine Tripterygium wilfordii.It has good anti-cancer,anti-inflammatory and immunosuppressive effects,and is clinically used to treat autoimmune diseases such as tumors,rheumatoid arthritis and systemic lupus erythematosus.However,triptolide itself has serious reproductive toxicity,which can cause a decrease in sperm count and vitality,as well as direct damage to the testicles,ovaries and uterus.The reproductive toxicity mechanism of triptolide is mainly related to oxidative stress and mito⁃chondrial damage.In addition,it is closely related to abnormal expressions of proteins such as breast cancer resistance protein(BCRP),peroxisome proliferator-activated receptors(PPAR)and cysteine protease-3.Decreased activity of Sertoli cell marker enzymes,mesenchymal cell marker enzymes,spermatogenic epithelial cell marker enzymes,mitochondrial marker enzymes,and lysosomal marker enzymes will also lead to reproductive toxicity.Researchers try to alleviate the reproductive toxicity of triptolide by studying triptolide drugs,modifying their chemical structure,and developing new drug delivery systems.This article reviews the latest research progress in the reproductive toxicity,toxicity mecha⁃nism and mitigation measures of triptolide.It is expected to provide reference for rational clinical appli⁃cations of this active ingredient.