从调节ATF6/c-fos信号通路研究淫羊藿苷改善衰老睾丸支持细胞功能衰退的分子机制

睾丸支持细胞（Sertoli细胞）功能衰退与衰老睾丸生殖功能减退密切相关，因而改善Sertoli细胞功能是延缓生殖衰老的关键之一；淫羊藿苷可显著延缓衰老睾丸生殖功能减退、改善Sertoli细胞功能，但其分子机制仍未阐明。研究显示，ATF6失活与Sertoli细胞功能衰退、生精障碍密切相关；新近研究发现，c-fos蛋白表达受ATF6调控，且c-fos是调节Sertoli细胞功能的关键分子，其表达下降与睾丸衰老直接相关，说明ATF6/c-fos通路是调节Sertoli细胞功能的关键途径。预实验结果显示，淫羊藿苷可提高Sertoli细胞ATF6表达，提示调节ATF6/c-fos通路可能是其改善Sertoli细胞功能的主要机制。据此，我们拟采用在体、离体实验相结合，运用qPCR、免疫荧光和siRNA等技术，从调节ATF6/c-fos通路的角度，研究淫羊藿苷改善Sertoli细胞功能衰退的分子机制。

The decline in testicular Sertoli cell function is associated with aging related reproductive dysfunction, and improving Sertoli cell function is one of the key factors to delay reproductive aging. Icariin can significantly delay the decline of spermatogenic function of aging testis and improve testicular Sertoli cell function. However, its molecular mechanism has not been elucidated. Research shows that the inactivation of activated transcription factor 6 (ATF6) is closely related to the decline of testicular Sertoli cell function and spermatogenesis. In addition, c-fos, a target gene of ATF6, is the key molecule to regulate the function of Sertoli cell. The decreased expression of c-fos is directly related to testicular aging, suggesting that ATF6/c-fos signal is the key pathway to regulate the function of Sertoli cell. Our preliminary experimental results show that icariin increased the expression of ATF6 in testicular Sertoli cell of aging rats, indicating that regulation of ATF6/c-fos signaling pathway may be the main molecular mechanism to improve the function of Sertoli cell. Based on this, combining a natural aging rats model with Sertoli cell in vitro model, we propose to investigate whether the improvement effects of icariin on the decline of Sertoli cell function with aging are associated with regulation of ATF6/c-fos signaling pathway by qPCR, immunofluorescence and siRNA techniques.