基于多巴胺信号通路探讨疏肝益胆方调控DAR/DAT治疗早泄的作用机制研究

早泄是常见的性功能障碍之一，其发生与多巴胺（DA）、五羟色胺（5-HT）等信号通路相关。前期研究证实疏肝益胆方治疗早泄安全有效，网络药理学提示疏肝益胆方可作用于多巴胺信号通路的DAR/DAT等环节。由此提出疏肝益胆方通过调控DA转运蛋白、D2、D3受体等物质的功能及含量，使突触间隙DA达到一个新的微平衡，从而延长早泄患者及大鼠射精潜伏期的假说。研究拟临床上通过随机对照试验观察疏肝益胆方干预早泄患者，检测干预前后的DA水平；同时通过吡贝地尔构建动物模型，采用不同剂量疏肝益胆方进行干预研究，观察大鼠的射精潜伏期等行为学指标，运用ELISA、qRT-PCR、荧光染色法等检测脑浆中多巴胺、多巴胺D2及D3受体、多巴胺转运体蛋白含量、多巴胺受体及多巴胺转运体基因表达水平，探讨疏肝益胆方治疗早泄的可能靶点，阐明D2、D3受体、DA转运体在调控射精中的作用机制，为疏肝益胆方在临床治疗早泄提供理论支撑。

Premature ejaculation is one of sexual dysfunction that is related to dopamine (DA), serotonin (5-HT) and other signaling pathways. Previous studies had confirmed that Shuganyidanfang was safe and effective for treatment of premature ejaculation. Network pharmacology suggests that Shugan yidanfang can be used on DAR/DAT of dopamine signaling pathway. Therefore, a hypothesis was put forward that Shuganyidanfang could prolong ejaculation latency of premature ejaculation patients and rats by regulating the functions and contents of DA transporters, D2 and D3 receptors and making a new micro-balance of DA in synaptic space. A randomized controlled trial was used on premature ejaculation patients who treated with Shuganyidanfang and control. DA level was tested before and after intervention. At the same time, rats model were established by pipemidil, than were treated with different doses of Shuganyidanfang. The behavioral indexes of IELT in rats were observed. Meantime, dopamine, dopamine D2, D3 receptors and dopamine transporter gene expression levels in rats’ brains were detected by using ELISA, qRT, PCR and fluorescence staining. The study are used to explore potential targets of Shuganyidanfang treating premature ejaculation, to clarify the mechanism of D2, D3 receptors and DA transporters in regulating ejaculation, and to provide theoretical support for Shuganyidanfang in clinical treatment of premature ejaculation.