因年龄增高导致的睾丸生精功能减退与生育缺陷已成为当前急需解决的生殖健康问题。我们前一个基金项目研究结果显示，五子衍宗丸能显著改善环磷酰胺所致睾丸生精障碍，其机制与抗氧化损伤与促进DNA损伤修复相关；近期研究发现，五子衍宗丸能显著改善衰老大鼠睾丸生精功能，且对Sertoli细胞功能有调节作用。相关研究显示，内质网应激损伤与Sertoli细胞功能、睾丸生精障碍直接相关；预实验结果显示，五子衍宗丸对内质网应激相关蛋白GRP78、 CHOP等有调节作用，提示五子衍宗丸可能通过减轻内质网应激损伤、改善Sertoli细胞功能，从而减缓睾丸生精功能衰退。本项目拟采用自然衰老大鼠与体外培养Sertoli细胞模型相结合，运用流式细胞分析、免疫荧光、SiRNA等技术，从调节内质网应激与Sertoli细胞功能角度，研究五子衍宗丸改善衰老所致睾丸生精功能减退的作用与机制，为临床防治男性生殖障碍提供科学依据。

The reproductive function decline and birth defects with advancing age have become an urgent issue for reproductive health. Our previous fund program demonstrated that wuziyanzong pills significantly improved the spermatogenic impairment induced by cyclophosphamide, which is related with its effects of anti-oxidative injury and DNA damage repair. Our recent studies showed that wuziyanzong pills significantly improved the spermatogenic dysfunction of aging, and improved the function of Sertoli cells of aging rats.The related research showed that endoplasmic reticulum stress damage was directly related to Sertoli cells damage and reproductive disorders. Our preliminary experimental results showed that wuziyanzong pills has the effect of regulation on endoplasmic reticulum stress-related proteins, including GRP78 and CHOP, suggesting wuziyanzong pills alleviates endoplasmic reticulum stress injury and improves the Sertoli cell function, thus delaying reproductive decline. In this project, in both a natural aging rats model and Sertoli cells in vitro model, we investigate whether the improvement effects of wuziyanzong pills on the decline of Sertoli cells and reproductive function of aging are related with regulation of endoplasmic reticulum stress by flow cytometry, immunofluorescence, SiRNA technology. These data will clarify the molecule mechanism of wuziyanzong pills on alleviation of male reproductive function with aging and provide a scientific basis for prophylaxis and therapy of testis aging.