AngII-p38MAPK信号通路在膀胱出口部分梗阻导致阴茎海绵体NOS异常表达中作用机制的研究

Most studies have suggested that partial bladder outlet obstruction (PBOO) was associated with the erectile dysfunction (ED). Our previous study has also found that the penis pressure induced by papaverine in PBOO adult rats were higher than those in control group. Some studies have suggestted that Ang II-p38 mitogen actived protein kinase (AngII-p38 MAPK) might be paticipated the pathogenesis of decrease erectile function induced by PBOO. High expression of AngII-p38MAPK in PBOO might interfence the nitric oxide synthase (NOS) abnormal expression in PBOO adult rats. To evaluate the mechanism of AngII-p38 MAPK, based on the preliminary studies , this study intends to measure the Ang II-p38 MAPK-NOS-related proteins expression, explore the relationships between the duration of PBOO and the Ang II-p38 MAPK-NOS-related proteins expression, and the mechanism of Ang II-p38 MAPK in the abnormal peins NOS expression induced by PBOO. They will provided the experimental evidences for the pathogensis of ED induced by PBOO.

多数研究提示勃起功能障碍（ED）的发病与膀胱出口部分梗阻（PBOO）相关，本课题组前期研究也证实PBOO成年大鼠罂粟碱诱导的阴茎海绵体内压较对照组出现显著下降。有研究发现血管紧张素II介导的p38丝裂原活化蛋白激酶（AngII-p38MAPK）可能参与PBOO所致ED的发病过程，其作用机制可能与调控阴茎海绵体一氧化氮合酶（NOS）的异常表达相关。因此为了进一步探索AngII-p38MAPK在PBOO导致阴茎海绵体NOS异常表达中的作用机制，本课题拟在前期研究基础上，（1）测定PBOO成年大鼠阴茎海绵体AngII-p38MAPK-NOS相关蛋白的表达；（2）探索AngII-p38MAPK在PBOO导致阴茎海绵体NOS异常表达中的作用机制；（3）探索PBOO建模后的不同时间与AngII-p38MAPK-NOS信号通路相关蛋白差异表达的关系。为进一步探究PBOO导致ED的发病提供实验依据。

勃起功能障碍（ED）是最常见的性功能障碍之一，既往研究提示膀胱出口部分梗阻（PBOO）与 ED的发病密切相关。有研究表明伴有PBOO症状的患者（如伴有前列腺增生、慢性前列腺炎），其ED的发病较正常对照组显著上升。长时间的PBOO将使膀胱平滑肌的特性和神经受体出现不可避免的改变，如继发下尿路出现高肾上腺素能状态，这将进一步诱导阴茎海绵体内平滑肌的损害，最终导致ED的发病。与此同时，多项研究也证实ED的发病与阴茎海绵体一氧化氮合酶（NOS）的表达相关。由于阴茎海绵体内NO的释放受到NOS的催化，同时NO作用于阴茎海绵体平滑肌的舒张，所以任何干扰阴茎海绵体NOS正常表达的因素均可能参与ED的发病。p38丝裂原活化蛋白激酶（p38MAPK）是细胞内重要的信号传导通路，在细胞凋亡、细胞因子产生及转录调节等过程中起着重要的作用。有研究发现p38MAPK信号传导通路参与阴茎海绵体NOS的表达。根据目前已完成的实验及取得的结果，发现PBOO成年大鼠阴茎海绵体内压较对照组（假手术组、非手术组）显著下降，PBOO建模后的不同时间成年大鼠阴茎海绵体内压间的差异具有显著统计学意义，PBOO建模大鼠模型建立成功。探索了PBOO建模的时间与阴茎海绵体AngII-p38MAPK-NOS相关蛋白差异表达间的联系；分析并阐述AngII-p38MAPK信号通路在PBOO导致阴茎海绵体NOS异常表达中的作用机制。本项目相关成果已经发表论文4篇（其中SCI论文3篇，中文期刊论文1篇），待发表SCI论文1篇，其他相应数据正在整理和撰写中，且多次参加国内外学术合作和交流，促进科研成果的传播，取得了良好的成效。