Zhang Kaishu, Ge Zhengyan, Fu Longlong, An Qi, Zhou Fang, Guo Ying, Wang Xiaowei, Lu Wenhong, Liang Xiaowei, Wang Shusong, Shang Xuejun, Gu Yiqun
Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Beijing 100730, China.
National Health and Family Planning Key Laboratory of Male Reproductive Health, Department of Male Clinical Research, National Research Institute for Family Planning & WHO Collaborating Center for Research in Human Reproduction, Beijing 100081, China.
Oncotarget. 2018 Apr 24;9(31):21770-21782. doi: 10.18632/oncotarget.24985.
At present, the treatment of oligoasthenospermia with western medicine is ineffective. Qilin pill (QLP) is a Chinese traditional medicine for treating male infertility. Recent multicenter clinical studies in China reported that QLPs markedly improved sperm quality. However, the mechanism of action of QLPs on oligoasthenospermia remains unknown. In this study, we investigated the mechanistic basis for improvement of semen parameters and reversal of testis damage by QLPs in a rat model of oligoasthenospermia induced by treatment with tripterygium glycosides (TGs) (40 mg/kg) once daily for 4 weeks. Rats were administered QLPs (1.62 g/kg or 3.24 g/kg) each day for 60 days, with untreated animals serving as controls. The concentration and motility of sperm extracted from rat epididymis were determined, whereas histopathological examination and immunohistochemical apoptosis analysis of rat testes was performed. Expression profiles of apoptosis-related genes were determined by microarray analysis; the results were validated by quantitative real-time PCR, western blotting, and immunohistochemistry. Sperm concentration and motility in the QLP treatment group were increased relative to those in control rats. Testis tissue and DNA damage were reversed by QLP treatment. The improvement function of QLPs on sperm and testis works mainly by suppressing mitochondrial apoptosis in the testis via modulation of B cell lymphoma (Bcl)-2, Bcl-2-associated X protein (Bax), cytochrome C, caspase-9 and caspase-3 expression. QLPs could improve sperm quality and testis damage in a rat model of oligoasthenospermia by inhibiting the Bax-Caspase-9 apoptosis pathway and exerting therapeutic effects.
目前，西医治疗少弱精子症效果不佳。麒麟丸是一种治疗男性不育症的中药。中国最近的多中心临床研究报告称，麒麟丸显著改善了精子质量。然而，麒麟丸治疗少弱精子症的作用机制尚不清楚。在本研究中，我们在雷公藤多苷（TGs）（40mg/kg）每日一次连续治疗4周诱导的少弱精子症大鼠模型中，研究了麒麟丸改善精液参数和逆转睾丸损伤的作用机制。大鼠每天给予麒麟丸（1.62g/kg或3.24g/kg），持续60天，未治疗的动物作为对照。测定从大鼠附睾提取的精子浓度和活力，同时对大鼠睾丸进行组织病理学检查和免疫组化凋亡分析。通过微阵列分析确定凋亡相关基因的表达谱；结果通过定量实时PCR、蛋白质印迹和免疫组化进行验证。与对照大鼠相比，麒麟丸治疗组的精子浓度和活力增加。麒麟丸治疗可逆转睾丸组织和DNA损伤。麒麟丸对精子和睾丸的改善作用主要通过调节B细胞淋巴瘤（Bcl）-2、Bcl-2相关X蛋白（Bax）、细胞色素C、半胱天冬酶-9和半胱天冬酶-3的表达来抑制睾丸中的线粒体凋亡。麒麟丸可通过抑制Bax-半胱天冬酶-9凋亡途径改善少弱精子症大鼠模型的精子质量和睾丸损伤，发挥治疗作用。
