阴茎勃起功能障碍（ED）严重危害男性身心健康，阴茎动脉血管功能障碍是其主要病因之一，但具体机制仍未完全阐明。项目组前期发现MYPT1是调节平滑肌收缩的核心蛋白，其表达水平在部分ED患者及ED模型小鼠（db/db）海绵体中显著下降；进一步筛选出的特异性上调MYPT1表达的药物莲心季氨碱，能够显著改善db/db小鼠的勃起功能。据此提出科学假说：MYPT1表达异常可引起阴茎动脉血管平滑肌收缩/舒张失调节，导致ED的发生。项目组将利用已构建的平滑肌特异性MYPT1敲除雄鼠，系统解析其性行为特征、阴茎生理功能、血管平滑肌收缩分子通路、RLC磷酸化水平等，阐明MYPT1表达下调诱发ED的分子机制；同时通过结构预测、分子交互实验等阐明莲心季氨碱通过上调MYPT1表达改善ED症状的作用机制。本项目的完成将揭示ED新的发病机理，为临床治疗提供有效靶标。

Erectile dysfunction (ED) has a serious impact on physical and mental health of males. The dysfunction of penile artery is one of the most vital factors in ED development; however, its mechanism remains unknown. Our previous research found that MYPT1 acted as a key protein in regulating the smooth muscle contraction，and the expression of MYPT1 in corpus cavernosum was significantly decreased in partly ED patients and db/db mice. Furthermore, we found that loutine could up-regulate the expression of MYPT1 and improve the erection in db/db mice. Therefore, we propose that the down-regulation of MYPT1 in penile artery may lead to the dysfunction of artery contraction/relaxation and consequent ED occurrence. Based on our prior work, we will further reveal the mechanism of MYPT1-related-ED by systematical evaluation of sexual behaviors, penile physiological function, the pathway of regulation in smooth muscle contraction/relaxation and RLC phosphorylation by using constructed MYPT1SMKO male mice; meanwhile, we will reveal the mechanism underlying the effect of loutin on ED phenotype by structural prediction and biomolecular interaction analysis. The completion of this project will clarify the novel pathogenesis of ED and provide a potential target for the disease treatment.