维生素D介导的TPH2影响5-HT合成在中枢神经系统射精调控中的作用及机制研究

早泄（PE）是最常见的男性性功能障碍，发病机制尚不明确，目前认为其发病与中枢神经递质5-羟色胺（5-HT）密切相关。研究发现色氨酸羟化酶-2（TPH2）是中枢5-HT合成过程的唯一限速酶，其活性受到维生素D（VitD）调控。本课题组初步研究证实，原发性早泄（LPE）患者TPH2基因呈现出显著多态性；预实验通过构建LPE大鼠模型发现其脑组织TPH2的表达明显低于对照组。因此我们推测VitD介导的TPH2可能通过影响5-HT的合成参与PE的发病。本课题拟通过构建TPH2基因敲除和VitD缺乏动物模型，分别从个体水平探讨VitD介导的TPH2对射精调控的影响，从组织水平探讨TPH2及5-HT在中枢脑组织中的差异表达与性行为的相关性，再通过体外细胞实验进一步验证VitD介导的TPH2调控5-HT的合成，从而揭示上述信号通路在中枢射精调控中的作用，为探索早泄的发病机制及治疗新途径提供理论依据。

Premature ejaculation (PE) is the most common sexual dysfunctions among men. However，the etiology and pathogenesis of PE are still unknown. At present, it is believed that its pathogenesis is closely related to the neurotransmitter 5-hydroxytryptamine (5-HT). Studies have found that tryptophan hydroxylase-2(TPH2) is the only rate-limiting enzyme in the synthesis of central 5-HT, and its activity is regulated by vitamin D (VitD). The preliminary research of our research group confirmed that the TPH2 gene in patients with primary premature ejaculation (LPE) showed significant polymorphism, and our pre-experiment found that the expression of TPH2 in brain tissue was significantly lower than that in control group through the construction of LPE rat model. Therefore, we speculate that TPH2 mediated by VitD may participate in the pathogenesis of PE by affecting the synthesis of 5-HT. In this project, we will construct animal models of TPH2 gene knockout and VitD deficiency, and discuss the effects of VitD-mediated TPH2 on ejaculation function regulation from the individual level, and the correlation between the differential expression of TPH2 and 5-HT in central brain tissue and sexual behavior from the tissue level. Furthermore, we will further verify the effects of VitD-mediated TPH2 on 5-HT synthesis through in vitro cell experiments, thus revealing the role of the above signal pathway in central ejaculation regulation and providing theoretical basis for exploring the pathogenesis and new therapeutic approaches of premature ejaculation.