基于“肾主生殖”理论研究补肾填精法通过StAR调控Leydig细胞功能的作用机制

The theory of “kidney dominating reproduction” is a high-level overview of reproductive physiology. Leydig cells, which produce testosterone, play an important role in the male reproductive system. It is recently found that steroidogenic acute regulatory protein (StAR) can inhibit cell apoptosis, and promote Leydig cell synthesis of testosterone. Previously, we demonstrated that kidney reinforcing drug, Yangjing capsule, can inhibit Leydig cell apoptosis, promote Leydig cells secreting testosterone, while up-regulate the expression of StAR. Therefore, we hypothesized that kidney reinforcing medicine could inhibit cell apoptosis, enhance testosterone synthesis in Leydig cells through up-regulation of StAR. This study intends to use aged mice with low testosterone, cell experiments, and small RNA interference (siRNA) technology to further study the effect of kidney reinforcing drug on the location and promotor of StAR. Then it can be identified that whether it is through the role of StAR to inhibit apoptosis of Leydig cells and promote the testosterone synthesis. The molecular mechanisms would be clarified that kidney reinforcing medicine on Leydig cell function. In conclusion, the study would contribute to elaborate the scientific connotation of “kidney dominating reproduction”, and use Chinese medicine to treat reproductive system diseases caused by low testosterone.

中医“肾主生殖”理论是对生殖生理的高度概括。Leydig细胞能合成睾酮，在男性生殖系统中发挥重要作用。近年发现，类固醇激素合成急性调节蛋白StAR能抑制细胞的凋亡，促进Leydig细胞合成睾酮。前期的研究表明，补肾填精中药一养精胶囊能抑制Leydig细胞的凋亡，促进睾酮合成，同时能上调StAR的表达。课题组推测补肾填精中药可能是通过StAR来调控Leydig细胞凋亡和睾酮合成功能。本研究拟利用睾酮低下老年小鼠、细胞实验及小RNA干扰（siRNA）技术，进一步研究补肾填精中药对StAR定位和StAR上游启动子的影响，明确其抑制Leydig细胞的凋亡，促进睾酮合成，是否是通过StAR发挥作用，进而阐明补肾填精中药调控Leydig细胞功能的分子机制。这对于揭示“肾主生殖”的科学内涵，应用中医药治疗睾酮低下引起的生殖系统疾病，具有重要的理论和现实意义。

中医“肾主生殖”理论对生殖疾病的诊治具有重要指导意义。前期的研究表明，补肾填精中药一养精胶囊能抑制Leydig细胞的凋亡，促进睾酮合成，同时能上调StAR的表达。课题组推测补肾填精中药可能是通过StAR来调控Leydig细胞凋亡和睾酮合成功能。本研究利用睾酮低下老年小鼠、细胞实验及小RNA干扰（siRNA）技术，明确其具体作用机制。结果表明，养精胶囊可以在动物水平，上调睾酮低下老年小鼠睾丸中StAR表达，下调Leydig细胞凋亡基因的表达，进而抑制细胞凋亡，促进睾酮的分泌。在体外细胞水平，养精胶囊可以激活StAR启动子活性，上调Leydig细胞中StAR的表达，调控凋亡相关基因bcl-2、bax、caspase-3的表达，抑制Leydig细胞的凋亡，促进Leydig细胞合成睾酮。本项目明确了“肾主生殖”与细胞凋亡和睾酮合成的关系，阐述中医基本理论的科学内涵，并为临床运用中药治疗睾酮低下引起的男科疾病提供指导作用。