基于“肾藏精”理论研究补肾填精法通过LncRNAH19调控StAR促进睾酮合成的作用机制

The "Kidney storing essence" theory is closely related to the function of testosterone. Kidney-reinforcing method can promote the synthesis of testosterone. While the specific mechanism is unclear. It is recently found that LncRNA H19 can regulate the function of microRNA Let-7, increase the expression of steroidogenic acute regulatory protein StAR, and promote testosterone level of Leydig cell. Previous studies have shown that Kidney-reinforcing formula, Yangjing capsule, can up-regulate the expression of StAR in Leydig cells, inhibit apoptosis and promote testosterone production. Consequently, we hypothesized Yangjing capsule could regulate H19 to promote StAR expression, inhibit Leydig cell apoptosis, and increase testosterone synthesis. In this study, based the theory of "Kidney storing essence", the effects of Yangjing capsule on the expression of H19 and Let-7 were studied, which can identify the molecular mechanism of Yangjing capsule on StAR and testosterone synthesis, by using the testosterone deficiency aged mice, in vitro cell experiment and RNA interference. This is important to clarify the specific mechanism of tonifying the kidney to promote the production of testosterone, reveal the theory of "Kidney storing essence", and apply Chinese medicine for improving testosterone, which has important theoretical value and clinical significance.

“肾藏精”理论与睾酮的功能密切相关，补肾填精法能够促进睾酮的合成，但其具体机制不清楚。近期发现，LncRNAH19可以调控microRNALet-7功能，提高类固醇快速调节蛋白StAR的表达，进而促进Leydig细胞合成睾酮。前期的研究表明，补肾填精中药养精胶囊可以上调Leydig细胞中StAR的表达，抑制细胞凋亡，促进睾酮生成。课题组推测养精胶囊可能是通过H19调控StAR的表达，抑制Leydig细胞凋亡，促进睾酮合成。本研究基于“肾藏精”理论，利用睾酮低下老年模型小鼠、体外细胞实验及RNA干扰技术，进一步研究养精胶囊对H19、Let-7表达的影响，明确其促进StAR表达和睾酮合成的分子机制。这对于明确补肾填精法促进睾酮生成的具体机制，阐明“肾藏精”理论，应用中医药提高睾酮合成，具有重要的理论价值和临床意义。

“肾藏精”理论与睾酮的生理功能密切相关，补肾填精法能够促进睾酮的合成，但具体机制不详。前期的研究表明，补肾填精中药养精胶囊可以上调Leydig细胞中StAR的表达，抑制细胞凋亡，促进睾酮生成。课题组推测养精胶囊可能是通过H19调控StAR的表达，进而促进睾酮合成。本研究利用睾酮低下老年小鼠、体外细胞实验及RNA干扰技术，明确其具体作用机制。结果表明，在动物水平养精胶囊可以上调睾酮低下老年小鼠睾丸中H19表达，下调MicroRNA Let7含量，并促进StAR表达，增加小鼠血清T和FT的浓度。在体外细胞水平，养精胶囊可以通过H19调控StAR表达，抑制Leydig细胞凋亡，促进睾酮生成。下调H19的表达，可以显著降低养精胶囊促进StAR合成睾酮的功效。这证实了养精胶囊能够通过LncRNA H19调控StAR，进而促进睾酮合成。本项目明确了养精胶囊促进睾酮生成的分子机理，阐明了补肾填精法改善男性生殖功能的具体机制。这对于揭示“肾藏精”的科学实质，指导临床治疗睾酮降低引起的生殖疾病，提高男性的生殖健康具有重要价值。