Toxic effects of Tripterygium wilfordii Hook F on the reproductive system of adolescent male rats
Toxic effects of Tripterygium wilfordii Hook F on the reproductive system of adolescent male rats
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DOI：
10.1016/j.biopha.2017.09.038
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发表时间：
2017-11-01
影响因子：
7.5
通讯作者：
He, Li
中科院分区：
文献类型：
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作者：
Jing, Xiaoping;Cheng, Weiwei;He, Li
雷公藤雷公藤多甙（TWHF）是从雷公藤（雷神藤）中提取的一种化合物，已在临床实践中用于治疗各种免疫相关疾病，特别是在儿科。然而，临床资料表明雷公藤多甙（GTW）对男性生殖系统有毒性作用，但其作用机制尚不清楚。在此，给予高剂量GTW 4周和低剂量GTW 12周可降低青春期雄性大鼠的体重和睾丸重量。这种作用伴随着血清睾酮水平的显著降低。值得注意的是，短期使用高剂量GTW或长期使用低剂量GTW会导致青春期雄性大鼠睾丸损伤。此外，类固醇生成急性调节蛋白（星星）、P450侧链裂解酶（P450 SCC）、细胞色素P450 17-羟化酶（P450 c17）、3 β-羟基类固醇脱氢酶（3 β-hydroxysteroiddehydrogenase，3 β-hydrosteroidase-steroidase-oxidase，3 β-hydroxysteroidase-oxidase，3 β-hydrosteroidase-steroidase-oxidase，3 β-（3 β-HSD），和17 β-羟基类固醇脱氢酶睾丸中的（17 β-HSD）mRNA和蛋白质通过高剂量GTW短期处理和低剂量GTW长期处理下调。因此，GTW通过抑制参与睾酮合成的关键酶的表达和总胆固醇水平，以浓度和时间依赖性的方式表现出雄性生殖毒性。
Tripterygium wilfordii Hook F. (TWHF) is a compound extracted from Lei Gong Teng (Thunder God Vine) that has been used to treat a variety of immune-related diseases in clinical practice, particularly in pediatrics. Nevertheless, clinical data indicated that glycosides from Tripterygium wilfordii Hook F (GTW) are toxic to the male reproductive system, but the mechanism is unknown. Here, the administration of a high dose of GTW for 4 weeks and a low dose for 12 weeks can reduce the body weights and testes weights in adolescent male rats. This effect is accompanied by a significantly reduction in the serum testosterone levels. Notably, short-term use of high-dose GTW or long-term use of low-dose GTW leads to testicular damage in adolescent male rats. Furthermore, the expression of the steroidogenic acute regulatory protein (StAR), P450 side chain cleavage enzyme (P450scc), cytochrome P450 17-hydroxylase (P450c17), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) mRNAs and proteins in the testes was down-regulated by a short-term treatment with high-dose GTW and a long-term treatment with low-dose GTW. Therefore, GTW exhibit male reproductive toxicity in a concentration-and time-dependent manner by inhibiting the expression of the key enzymes and total cholesterol level involved in testosterone synthesis.