Fan Yuan-Fang, Xu Ying, Su Xiao-Hui, Liu Li-Ling, Tian Ya-Ge, Zhao Yuan, Kong Xiang-Ying, Lin Na
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2020 Feb;45(4):755-763. doi: 10.19540/j.cnki.cjcmm.20190523.401.
The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets on the reproductive system of Ⅱ type collagen induced arthritis(CIA) male rats, and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group(Con), model group(CIA), Tripterygium Glycosides Tablets clinical equivalent dose groups of 1, 2, 4 times(9, 18, 36 mg·kg~(-1)), 10 rats in each group, and were given by gavage once a day for 42 days after the first immunization. The organ index of testis and epididymis were calculated on days 21 and 42. Histopathological and morphological changes of testis and epididymis were observed under optical microscope. Sperm count, sperm malformation rate and sperm kinetic parameters in epididymal tissues were observed by computer assisted sperm analysis(CASA). The concentration of testosterone(T), nitric oxide synthase(NOS) and aromatase(CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of testis and epididymis. The results showed that, compared with Con group, CIA group significantly increased the rate of testicular spermatogenic tubule lesion and sperm malformation, decreased the average path speed, and no significant changes were observed in other groups. Tripterygium Glycosides Tablets at 4 times clinical equivalent dose can significantly reduce the testis index(P<0.01), each dose group can reduce the epididymis index(P<0.05). Each dose group of Tripterygium Glycosides Tablets could cause different degrees of damage to the testis and epididymis, the proportion of testicular histopathology lesions increased, the number of spermatogenic cells in the seminiferous tubules decreased, and so on. It could reduce the number of sperm, increase the rate of sperm deformity, make the parameters of sperm dynamics abnormal, and so on. Tripterygium Glycosides Tablets at 4 times dose could significantly reduce the content of serum sex hormone T and key enzyme of androgen synthesis(P<0.05 or P<0.01), but had no effect on CYP19 A1. The expression of Bax and Bcl-2 in testis and epididymis were increased by 2 and 4 times doses of Tripterygium Glycosides Tablets(P<0.05, P<0.01 or P<0.01). The results showed that 21 d administration of Tripterygium Glycosides Tablets at equal or higher doses could induce obvious toxic effect to the reproductive organs of CIA male rats, and lower the level of serum sex hormone T and the key enzyme of androgen synthesis, NOS. The mechanism of abnormal changes of Bax and Bcl-2 in Testis and epididymis is still to be elucidated.
本文旨在观察雷公藤多苷片对Ⅱ型胶原诱导性关节炎（CIA）雄性大鼠生殖系统的毒性作用，并初步探讨其毒性机制。将50只SD大鼠随机分为正常对照组（Con）、模型组（CIA）、雷公藤多苷片临床等效剂量1倍、2倍、4倍（9、18、36 mg·kg⁻¹）组，每组10只，首次免疫后每天灌胃给药1次，连续给药42天。于第21天和第42天计算睾丸和附睾的脏器指数。光镜下观察睾丸和附睾的组织病理学及形态学变化。采用计算机辅助精子分析（CASA）观察附睾组织中的精子计数、精子畸形率及精子运动参数。采用酶联免疫吸附测定（ELISA）检测血清睾酮（T）、一氧化氮合酶（NOS）及芳香化酶（CYP19 A1）的浓度。采用免疫组织化学法观察睾丸和附睾凋亡途径中Bax和Bcl-2相关蛋白的表达。结果显示，与Con组相比，CIA组睾丸生精小管病变率及精子畸形率显著升高，平均路径速度降低，其他组未见明显变化。雷公藤多苷片4倍临床等效剂量可显著降低睾丸指数（P＜0.01），各剂量组均可降低附睾指数（P＜0.05）。雷公藤多苷片各剂量组均可对睾丸和附睾造成不同程度损伤，睾丸组织病理学病变比例增加，生精小管中生精细胞数量减少等。可使精子数量减少，精子畸形率升高，精子动力学参数异常等。雷公藤多苷片4倍剂量可显著降低血清性激素T及雄激素合成关键酶的含量（P＜0.05或P＜0.01），但对CYP19 A1无影响。雷公藤多苷片2倍和4倍剂量可使睾丸和附睾中Bax和Bcl-2的表达升高（P＜0.05、P＜0.01或P＜0.01）。结果表明，给予等效或更高剂量雷公藤多苷片21天可对CIA雄性大鼠生殖器官产生明显毒性作用，降低血清性激素T水平及雄激素合成关键酶NOS水平。睾丸和附睾中Bax和Bcl-2异常变化的机制尚待阐明。
