PDGF介导PI3K/AKT/β-catenin通路调控阴茎海绵体神经损伤后平滑肌缝隙连接的机制研究

Erectile dysfunction (ED) is a common complication after radical prostatectomy (RP), cavernous nerves injury during the process and hypoxia in penis was thought to be one of the most important causes. Gap junction (GJ) is one of the most important physiology foundations of smooth muscle cell synchronous excitation and fast coordinated contract and relax, which plays an important role during erectile process, and date showed that hypoxia will lead to GJ dysfunction. Our previous date showed that there are different degrees of hypoxia in rats penis with bilateral cavernous neurectomy (BCN), and the distribution of GJ and expression of Cx43 are also changed. In order to define the changes and the specific molecular mechanism of GJ in BCN model and the smooth muscle cell hypoxia model, we will use the knockout rats, siRNA transfection, transmission electron microscopy and other techniques to active or inhibit platelet derived growth factor (PDGF) and PI3K/AKT/β-catenin pathway, to observe the impact of hypoxia on GJ function and the level of Cx43, as well as the PI3K/AKT/β-catenin pathway in Cx43 regulation. The research results can be helpful to the further understanding of the pathological mechanism in ED patients after RP, and provide new theoretical basis and strategy for clinical diagnosis and treatment.

阴茎勃起功能障碍（ED）是前列腺癌根治术（RP）后常见并发症，其中阴茎海绵体神经损伤导致局部组织缺氧认为是难治性ED发生的重要原因之一。缝隙连接（GJ）作为平滑肌细胞同步舒缩的生理基础，在阴茎的勃起过程中起着重要作用，相关研究表明缺氧可导致GJ改变。课题组前期研究发现大鼠双侧海绵体神经切除动物模型海绵体组织中存在着缺氧情况、GJ变化及其组成蛋白Cx43表达的异常。为了明确海绵体神经损伤后海绵体中GJ的变化及其机制，本项目拟采用先前建立的细胞缺氧及双侧海绵体神经切除动物模型，通过基因敲除小鼠、siRNA转染、过表达质粒等方法激活或抑制PDGF及PI3K/AKT/β-catenin通路，观察GJ、Cx43的影响，明确PDGF激活的PI3K/AKT/β-catenin途径对Cx43的调控作用。研究成果将有助于深入了解RP术后ED发生发展的病理过程，为临床诊疗提供新的理论依据。

阴茎勃起功能障碍(ED)是前列腺癌根治术(RP)后常见并发症，其中阴茎海绵体神经损 伤导致局部组织缺氧认为是难治性ED发生的重要原因之一缝隙连接(GJ)作为平滑肌细胞同 步舒缩的生理基础,在阴茎的勃起过程中起着重要作用,相关研究表明缺氧可导致GJ改变 课 题组前期研究发现大鼠双侧海绵体神经切除动物模型海绵体组织中存在着缺氧情况 GJ变化及其组成蛋白Cx43表达的异常为了明确海绵体神经损伤后海绵体中GJ的变化及其机制，本项目首先用先前建立的细胞缺氧及双侧海绵体神经切除及夹损伤动物模型,过表达等方法激活或抑制PDGF及PI3K/AKT/β-catenin通路,观察GJ Cx43的影响,明确PDGF激活的PI3K/AKT/β-catenin途径对缝隙连接蛋白Cx43的调控作用研究成果将有助于深入了解RP术后ED发生发展的病理过程，为临床诊疗提供新的理论依据。同时我们在基于上述基础引入中医益气活血法治疗ED，以期从中寻找中医治疗ED的新靶点