Cai Jiayu, Song Lingxiong, Hu Zebo, Gao Xiaojiao, Wang Yuhan, Chen Yang, Xi Ke, Lu Xin, Shi Yonghui
Traditional Chinese Medicine Department, Jinling Hospital, Nanjing 210002,China.
Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing, China.
Heliyon. 2024 Oct 3;10(19):e38778. doi: 10.1016/j.heliyon.2024.e38778. eCollection 2024 Oct 15.
Oligoasthenospermia (OAS) is a global human developmental disease and the most common type of male infertility. There are currently no sufficiently effective therapeutic strategies for OAS. Pill (WZYZP) is a traditional Chinese prescription for the clinical treatment of male infertility, and its efficacy is well known in China. Therefore, due to the complexity of traditional Chinese medicine, the specific mechanism of action of WZYZP on OAS has not been elucidated. Astragalin (AG), one of the main active substances in WZYZP, has good antioxidant effect. The aim of this research is to investigate whether AG, the active substance in WZYZP, can treat OAS by promoting Nrf2 nuclear translocation and inhibiting ferroptosis. The OAS model was established by intraperitoneal injection of cyclophosphamide, and the therapeutic effects of AG and WZYZP on OAS were evaluated by detecting sperm quality, sex hormone levels and testicular pathological changes after intragastric administration of AG and WZYZP. Western blot was used to measure the expression levels of TFR1, SLC7A11, GPX4 and FTH1. The nuclear translocation of Nrf2 was detected by immunofluorescence staining and nuclear/intracellular expression of Nrf2. The results showed that AG could improve sperm quality and serum sex hormone levels in OAS rats, reduce the expression of testicular Fe and TFR1, up-regulate testicular SLC7A11, GPX4 and FTH1, and inhibit testicular ferroptosis. At the same time, AG can promote the expression and nuclear translocation of Nrf2 in the testis of OAS rats. AG can alleviate OAS via promoting nuclear translocation of Nrf2 and inhibiting ferroptosis of testis.
少弱精子症（OAS）是一种全球性的人类发育疾病，也是男性不育最常见的类型。目前对于OAS尚无足够有效的治疗策略。五子衍宗丸（WZYZP）是临床治疗男性不育的传统中药方剂，其疗效在中国广为人知。然而，由于中药的复杂性，WZYZP对OAS的具体作用机制尚未阐明。黄芪甲苷（AG）是WZYZP中的主要活性成分之一，具有良好的抗氧化作用。本研究旨在探讨WZYZP中的活性成分AG是否能通过促进Nrf2核转位和抑制铁死亡来治疗OAS。通过腹腔注射环磷酰胺建立OAS模型，通过检测AG和WZYZP灌胃给药后精子质量、性激素水平和睾丸病理变化来评估AG和WZYZP对OAS的治疗效果。采用蛋白质免疫印迹法检测TFR1、SLC7A11、GPX4和FTH1的表达水平。通过免疫荧光染色检测Nrf2的核转位以及Nrf2的核/细胞内表达。结果表明，AG可改善OAS大鼠的精子质量和血清性激素水平，降低睾丸中铁和TFR1的表达，上调睾丸中SLC7A11、GPX4和FTH1的表达，并抑制睾丸铁死亡。同时，AG可促进OAS大鼠睾丸中Nrf2的表达和核转位。AG可通过促进Nrf2核转位和抑制睾丸铁死亡来缓解OAS。
