迟发性性腺功能减退症(LOH)病发于男子“五八”-“八八”天癸渐竭之时，睾酮水平下降是主要原因，与睾丸间质细胞(Leydig cell)氧化应激、自噬下降诱导的细胞衰老有关，因而Leydig细胞睾酮合成功能随增龄衰退是关键研究因素。基于“天癸-睾酮”可能相关性，我们提出“天癸渐竭”的微观基础是增龄相关的Leydig细胞“ROS蓄积-线粒体自噬失调”。围绕Leydig细胞睾酮合成功能衰退，以“氧化应激-自噬”为切入点，开展以下研究：①Leydig细胞“ROS蓄积-线粒体自噬失调”是“天癸渐竭”的微观基础假说验证；②“天癸渐竭”理论指导的雄蚕益肾方调控Leydig细胞睾酮合成分子机制研究；③雄蚕益肾方调控Leydig细胞“ROS-线粒体自噬”干预LOH分子机制研究。本项目假说的验证，将从全新角度阐释和丰富“天癸竭”理论内涵，并为临床确立“补肾、益天癸”的LOH中医药治疗策略提供实验依据。

Late-onset Hypogonadism (LOH) is typically accompanied with reduced serum level of testosterone, which usually begins of Tian Guei failure is about “wu ba” to “ba ba”. With men aging, the functional decline of leydig cell is the core of the disease pathogenesis. The accumulation of Reactive oxygen species (ROS) and autophagy decline, both of which induced cell senescence of leydig cell may explain for occurrence of LOH. Based on the correlation of testosterone and Tian Guei, we suggested that the age-related accumulation of ROS and mitophagy decline in leydig cell, is the micro foundation of Tian Guei failure. We carried out the following researches around the functional decline of leydig cell, which with the key point of ROS and autophagy. ①The hypothesis validation of age-related accumulation of ROS and mitophagy decline in leydig cell, is the micro foundation of Tian Guei failure.②The molecular mechanism of Xiong can yi shen formula, which regulated testosterone biosynthesis in leydig cell. ③The molecular mechanism of Xiong can yi shen formula, which treatment LOH by regulated ROS and mitophagy in leydig cell. The study results will provide empirical evidence to support the theory of Tian Guei failure, and lay a substantial foundation for LOH treatment, which use the method of reinforcing kidney recipe.