雷公藤对雄鼠的生殖毒性研究进展

Reproductive toxicity of Tripterygll Radix in male rats

雷公藤具有清热解毒、祛风通络、舒筋活血等多种功效,对类风湿性关节炎、肾炎、红斑狼疮等疾病有一定疗效。雷公藤的主要活性成分为雷公藤甲素、雷公藤多苷、雷公藤内酯等。据报道雷公藤制剂具有一定的生殖毒性,对雄鼠生殖系统造成的损伤主要表现为异常形态的精子数量增加、精子的运动功能和活力降低;高剂量或长期用药还会使睾丸生精细胞脱落、数量减少甚至消失,从而影响精子的发生;降低睾丸酸性磷酸酶(ACP)、透明质酸酶(HAse)、琥珀酸脱氢酶(SDH)和磷酸果糖激酶1(PFK1)等相关酶的活性;抑制血清抑制素B(INHB)和睾酮合成所需的关键酶,从而对雄鼠产生生殖毒性。雷公藤的毒性机制主要与Herc4、Mrto4和Ipo11等基因表达异常及Bax、FasL等基因表达上调诱导的生精细胞和精子的凋亡相关,但其具体的信号通路尚不完全明确。本文可为雷公藤在临床上的安全使用提供参考。

Tripterygll Radix has a variety of effects such as clearing heat and detoxifying, dispelling wind and invigo-rating blood, which is effective in rheumatoid arthritis, nephritis and lupus erythematosus. The main active ingredients of Tripterygll Radix are triptolide, tripterygium glycosides and tripchlorolide. However, some reproductive toxicity has been reported for Tripterygll Radix preparations. The damage to the reproductive system of male rats caused by the Tripterygll Radix preparations was mainly characterized as increasing number of abnormally formed spermatozoa and decreasing sperm motility and viability. High doses or long-term use of the drug can also affect spermatogenesis by causing the exfoliation, decrease and even disappearance of testicular spermatogenic cells. Besides, it can reduce the activity of enzymes including testicular acid phosphatase(ACP), hyaluronidase(HAse), succinate dehydrogenase(SDH) and phosphofructokinase 1(PFK1). In addition, it inhibits serum inhibitor B(INHB) and key enzymes required for testosterone synthesis, resulting in reproductive toxicity in male rats. The mechanism of toxicity of Tripterygll Radix is mainly related to apoptosis of spermatogenic cells and spermatozoa induced by abnormal expression of genes such as Herc4, Mrto4 and Ipo11 and up-regulated expression of Bax and FasL, but the specific signaling pathways are not fully understood. This article can provide a reference for the safe use of Tripterygll Radix in clinical practice.