磷酸二酯酶（PDEs）在逼尿肌位相收缩及OAB发生发展中的作用和机制研究

环核苷酸磷酸二酯酶（PDEs）是细胞内降解环核苷酸（cAMP和cGMP）的蛋白水解酶。近年来，PDEs在疾病发生发展过程中的作用逐渐被人们所认识，其有些家族成员已成为心力衰竭、肺动脉高压和男性勃起功能障碍等疾病的治疗靶点。膀胱逼尿肌一个重要生理特性就是能产生自发节律性的位相收缩，其兴奋性异常是常见的膀胱功能障碍。我们前期的研究结果表明，PDE3和PDE4参与调控大鼠乳鼠膀胱逼尿肌的位相收缩，但其作用机制以及在膀胱过度活动症（overactive bladder, OAB）发生发展中的作用尚不清楚。因此，本项目拟从分子、细胞、逼尿肌组织及在体层面上，利用电生理、激光共聚焦显微成像、生物化学与分子生物学、药理学等技术方法，结合OAB模型及G-CaMPJ转基因小鼠，深入研究PDE3/4在膀胱逼尿肌位相收缩和OAB发生发展中的作用与机制，希望为OAB的防治提供理论基础及可能的、新的靶点。

Cyclic nucleotide phosphodiesterases (PDEs) superfamily, the enzymes to hydrolyze cAMP and cGMP, mediates a series of physiological and pathological processes. Recently, their roles in the occurrence and development of human disease have gradually been known and some PDE subfamily members have been recognized as potential targets for curing some of human diseases including heart failure, pulmonary hypertension, and erectile dysfunction. The urinary bladder is a hollow organ that stores and expels urine. One of the most important features of this muscle is its ability to generate considerable phasic contractions. Impairment of this ability is one of the most common bladder dysfunctions. Our previous study suggested that PDE3 and PDE4 are involved in the regulation of the phasic contractions of neonatal rat bladder detrusor SM. However, the underlying mechanisms are poorly understood. In the present study, we will deeply investigate the molecular mechanisms of PDE3/4 in mediating the phasic contraction of detrusor smooth muscle, using the transgenic animal model, electrophysiological, modern imaging, molecular and biomedical approaches. Moreover, we will also determine their role in overactive bladder (OAB) disease induced by partial bladder outlet obstruction.