内质网应激在肥胖雄性睾丸生精细胞凋亡中的作用及原花青素干预研究

Reproductive health is a crucial issue related to human self-sustainable development of mankind. Obesity appears to be associated with male reproductive dysfunction. However, the mechanisms involved are not fully clarified. It has been verified that oxidative stress induced testicular germ cell apoptosis play an important role in this process. Whether endoplasmic reticulum stress (ERS) which closely related to oxidative stress also involved in this process need further investigation. In recent years, people pay more attention to the relationship between the endoplasmic reticulum stress male reproductive dysfunction. Thus, based on recent research progress on obesity and male reproductive, oxidative stress, endoplasmic reticulum stress and testicular germ cell apoptosis, we put forward the hypothesis that endoplasmic reticulum stress mediates testicular cell apoptosis in is one important mechanism of obesity-induced male reproductive dysfunction. Procyanidins as natural antioxidants have protective effects on oxidative stress and endoplasmic reticulum stress-induced cell apoptosis, and it is not clear whether it has protective effect on obesity-induced testicular germ cell apoptosis need further study. In order to explore and further reveal the molecular mechanism of obesity induced male reproductive dysfunction and find effective way to protect male reproductive health. At present study, we will take high-fat diet induced obese rats model as subjects, inhibitors of ERS 4-phenyl butyrate(4-PBA) will be used to block ERS pathway and parameters as sperm quality, hormone levels and testicular germ cell apoptosis will be evaluated to assess protective effect of 4-PBA and procyanidins on obesity-induced testicular germ cell apoptosis. Real-time PCR and Western blot technology will be used to explore the mechanism of obesity-induced male reproductive dysfunction. The purpose of the current study is to provided a theoretical basis for the protection of male reproductive health.

肥胖能导致雄性生殖功能损伤，但其具体机制尚未完全阐明。氧化应激能诱发肥胖雄性睾丸生精细胞凋亡，与之关系密切的内质网应激是否参与其中尚待研究。基于肥胖与雄性生殖、内质网应激、氧化应激、睾丸生精细胞凋亡的研究进展，我们提出内质网应激诱导肥胖雄性睾丸生精细胞凋亡是其致雄性生殖功能损伤机制之一的假说。原花青素对氧化应激和内质网应激诱导的多种细胞凋亡有保护作用，其是否对肥胖雄性睾丸生精细胞凋亡具有保护作用尚不清楚。为验证该假说，拟以高脂膳食诱导营养性肥胖大鼠为研究对象，用内质网应激抑制剂4-苯基丁酸(4-PBA) 和原花青素干预，观察其对精子质量、性激素水平和生精细胞凋亡程度等的影响，研究4-PBA和原花青素对肥胖雄性睾丸生精细胞凋亡的拮抗作用，采用Real -time PCR、Western blot等技术，探讨内质网应激在肥胖致雄性睾丸生精细胞凋亡中的作用，为保护男性生殖健康提供理论指导。

肥胖能导致雄性生殖功能损伤，但其具体机制尚未完全阐明。氧化应激能诱发肥胖雄性睾丸生精细胞凋亡，与之关系密切的内质网应激是否参与其中尚待研究。本研究以高脂膳食诱导的营养性肥胖大鼠为研究对象，用内质网应激抑制剂4-苯基丁酸(4-PBA) 和原花青素干预研究，结果发现肥胖可导致血清睾酮水平下降、睾丸氧化应激水平升高、睾丸病理损伤、睾丸生精细胞凋亡水平增高、精子质量下降等生殖功能受损的现象；机制研究发现肥胖睾丸内质网应激通路被激活。4-苯基丁酸(4-PBA) 和原花青素干预可以减轻肥胖诱导的雄性生殖功能损伤；其机制可能与减轻氧化应激水平，继而降低睾丸内质网应激水平，从而减少睾丸生精细胞凋亡有关。