Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway
Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway
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小檗碱通过抑制 ROS/JAK2/NFκB 通路对糖尿病大鼠生殖功能和精子发生的保护作用
DOI：
10.1111/andr.12764
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发表时间：
2020-02-16
期刊：
影响因子：
4.5
通讯作者：
Jiang, Hongyang
中科院分区：
文献类型：
--
作者：
Song, Jingyu;Gao, Xintao;Jiang, Hongyang
背景糖尿病（DM）会导致男性生殖系统受损，被认为是部分解释男性不育的关键因素。因此，了解DM引起的不孕不育的机制将有助于确定新的治疗策略。 目的 阐明ROS/JAK2/NF kappa B通路在DM引起的生殖功能低下和精子发生受损中的作用。另外，探讨抑制ROS/JAK2/NF kappa B通路的单体小檗碱(BB)在DM所致不育发病机制中的保护作用。方法将12周龄雄性Sprague-Dawley大鼠分为4组：对照组、DM组、对照组+BB组、DM+BB组。链脲佐菌素用于诱导 DM。 BB治疗大鼠4周后，进行生育试验以考察其生殖功能，并通过显微镜评估睾丸重量和精子活力。通过 DHE 染色评估氧化应激。 TUNEL染色用于检测细胞凋亡状态。进行细胞实验以确定 BB 的体外作用。采用免疫组织化学、免疫荧光和蛋白质印迹法检测蛋白表达。结果我们的结果表明，DM大鼠的生殖功能低下，除了曲细精管受损外，还伴有睾丸重量和精子活力下降。然而，经 BB 治疗的 DM 大鼠的生殖功能参数有显着改善。随后，我们的数据显示，DM 大鼠睾丸中的 ROS 水平升高，从而激活 JAK2，进一步激活 NF kappa B 通路，导致睾丸细胞凋亡增加和受损。而BB可以减弱ROS的产生并消除JAK2/NF kappa B通路的激活，从而抑制DM大鼠睾丸细胞的凋亡。结论ROS/JAK2/NF kappa B通路参与了DM引起的生殖功能低下和生精受损。 BB可以通过抑制ROS/JAK2/NF kappa B通路对DM的生殖功能和精子发生发挥保护作用。
Background Diabetes mellitus (DM) induces impairment of male reproductive system and is considered as a key factor that could partially provide an explanation for male infertility. Thus, understanding the mechanism underlying DM-induced infertility will aid in the identification of novel therapeutic stratagems.Objectives To delineate the role of ROS/JAK2/NF kappa B pathway in DM-induced low reproductive function and impaired spermatogenesis. Additionally, to investigate the protective effect of monomeric Berberine (BB) that inhibits ROS/JAK2/NF kappa B pathway, in the pathogenesis of DM-induced infertility.Methods 12-week-old male Sprague-Dawley rats were divided into four groups: control group, DM group, control plus BB group, and DM plus BB group. Streptozotocin was used to induce DM. After treating the rats with BB for 4 weeks, fertility tests were conducted to investigate the reproductive function, and testis weight along with sperm motility was assessed through microscope. Oxidative stress was evaluated by DHE staining. TUNEL staining was utilized to detect the state of apoptosis. Cell experiments were carried out to define the role of BB in vitro. Immunohistochemistry, immunofluorescence, and Western blotting were employed to measure the protein expression.Results Our results indicate that the reproductive function of DM rats was low, accompanied by decreased testis weight and sperm motility in addition to the impairment of the seminiferous tubules. However, there was a significant improvement in the reproductive function parameters in the BB-treated DM rats. Subsequently, our data revealed that DM rats produce an increased level of ROS in the testis, which activates JAK2 further activating the NF kappa B pathway, leading to increased apoptosis and impaired cells in the testicles. However, BB could attenuate the ROS production and abrogate activation of JAK2/NF kappa B pathway, thus inhibiting the apoptosis in the testicular cells of DM rats.Conclusion ROS/JAK2/NF kappa B pathway is involved in the DM-induced low reproductive function and impaired spermatogenesis. BB can play a protective role in preserving the reproductive function and spermatogenesis in DM by inhibiting ROS/JAK2/NF kappa B pathway.