雷公藤甲素毒性作用及减毒研究的整合探析

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。

Side Effect and Attenuation of Triptolide

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.