雷公藤多苷的药理毒理作用研究进展

近年来,雷公藤多苷(TWP)在临床使用越来越广泛,多被用于治疗类风湿关节炎,还作为基本免疫抑制药物治疗各种肾脏疾病,如肾病综合征等,但其临床有多种不良反应事件发生,用药方案存在争议,尤其是使用剂量和使用时间。为了雷公藤多苷的临床合理使用和深入研究,综述其药理毒理研究进展。通过梳理近年来国内外有关雷公藤多苷的药理毒理研究文献,发现雷公藤多苷的药理作用研究多集中在抗炎、抗肿瘤、肾脏保护和免疫抑制方面,主要是通过调节核转录因子-κB(NF-κB)信号通路,雷帕霉素靶蛋白(m TOR)信号通路和细胞凋亡相关信号通路的细胞因子表达水平发挥药理作用;其毒理作用研究多集中在肝毒性、肾毒性和生殖系统毒性方面,毒性作用多与氧化应激反应和炎症因子表达相关。雷公藤多苷的主要活性成分研究集中在雷公藤内酯醇和雷公藤红素。雷公藤多苷药理毒理研究较深入,表明其效、毒存在剂量依赖性和时间依赖性,具有量-效、时-效、量-毒、时-毒关系,未见雷公藤多苷在功效背景下随使用剂量和时间变化的毒性研究,其关联机制仍需进一步深入研究与探讨。

Pharmacological and Toxicological Effect of Tripterygii Radix et Rhizoma Polyglycosides

In recent years,Tripterygii Radix et Rhizoma polyglycosides have been used more and more widely in clinic, mostly in the treatment of rheumatoid arthritis. Besides, it is also used as a basic immunosuppressive drug to treat various kidney diseases,such as nephrotic syndrome. However,there are many adverse reactions in clinic,as well as controversies over its medication regimen,especially its dosage and time. To make rational use of Tripterygii Radix et Rhizoma polyglycosides in clinic and further study,the pharmacological and toxicological research progress of Tripterygii Radix et Rhizoma polyglycosides was reviewed. The author collected pharmacological and toxicological research literatures of Tripterygii Radix et Rhizoma polyglycosides at home and abroad in recent years,finding that Tripterygii Radix et Rhizoma polyglycosides have the pharmacological effects of anti-inflammation, anti-tumor, kidney protection and immunosuppression, and mainly plays a pharmacological role by regulating the expression of cytokines in NF-κB signaling pathway,m TOR signaling pathway and apoptosis-related signaling pathway. And the toxicological effects of Tripterygii Radix et Rhizoma polyglycosides mostly focused on hepatotoxicity,nephrotoxicity and reproductive system toxicity,which are mostly related to oxidative stress response and expression of inflammatory factors. The main components of Tripterygii Radix et Rhizoma polyglycosides are triptolide and celastrol. The pharmacological and toxicological studies of Tripterygii Radix et Rhizoma polyglycosides are in-depth,the results showed that the efficacy and toxicity were dose-dependent and time-dependent,with no toxicity study of Tripterygii Radix et Rhizoma polyglycosides varying with dosage and time in the context of efficacy,indicating dose-effect,time-effect,dose-toxicity,time-toxicity relationships. Relevant mechanisms still need further study.