Hou Yi, Jia Linpei, Zhang Ying, Ji Wei, Li Hai
Department of Urology, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China.
Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing 100000, P.R. China.
Oncotarget. 2017 Nov 11;8(62):105692-105702. doi: 10.18632/oncotarget.22389. eCollection 2017 Dec 1.
Erectile dysfunction (ED) is a common complication of diabetes mellitus (DM). The exact role of the NGF/TrkA signaling pathway in the pathogenesis of diabetic ED is largely unknown. In the present study, we investigated the role of the NGF/TrkA signaling pathway in Sprague-Dawley rats with diabetic ED. Animals were divided into 2 groups: the normal group and the DM ED model group. The model group included the blank subgroup, the negative control (NC) subgroup, the TrkA subgroup and the TrkA + NGF subgroup. Erectile function, intracavernous pressure (ICP) and mean arterial pressure were measured respectively. Immunohistochemistry was used to examine the number of neuronal nitric oxide synthase (nNOS) expressing nerve fibers. The quantitative real-time polymerase chain reaction was applied to detect the mRNA expressions of NGF and TrkA in the cavernous tissue. Further, Western blotting was conducted to detect the expressions of NGF, TrkA and its downstream ERK pathway-related proteins. Higher erectile frequency, ICP values and diastolic function, more nNOS-positive nerve fibers, and decreased systolic function of the corpus cavernosum smooth muscle were found in the TrkA and TrkA+NGF groups when compared with the blank and the NC groups. Moreover, significantly higher mRNA expressions of NGF and TrkA, and upregulated protein expressions of NGF, TrkA, c-raf, ERK1/2 and CREB1 were found in the TrkA and the TrkA + NGF groups. In conclusion, downregulation in the NGF/TrkA signaling pathway may contribute to the pathogenesis of diabetic ED.
勃起功能障碍（ED）是糖尿病（DM）的常见并发症。NGF/TrkA信号通路在糖尿病性ED发病机制中的确切作用尚不清楚。在本研究中，我们调查了NGF/TrkA信号通路在患有糖尿病性ED的Sprague-Dawley大鼠中的作用。动物被分为两组：正常组和糖尿病性ED模型组。模型组包括空白亚组、阴性对照（NC）亚组、TrkA亚组和TrkA + NGF亚组。分别测量勃起功能、海绵体内压（ICP）和平均动脉压。采用免疫组织化学法检测表达神经元型一氧化氮合酶（nNOS）的神经纤维数量。应用定量实时聚合酶链反应检测海绵体组织中NGF和TrkA的mRNA表达。此外，进行蛋白质免疫印迹法检测NGF、TrkA及其下游ERK通路相关蛋白的表达。与空白组和NC组相比，TrkA组和TrkA + NGF组的勃起频率、ICP值和舒张功能更高，nNOS阳性神经纤维更多，海绵体平滑肌收缩功能降低。此外，TrkA组和TrkA + NGF组中NGF和TrkA的mRNA表达显著更高，NGF、TrkA、c-raf、ERK1/2和CREB1的蛋白表达上调。总之，NGF/TrkA信号通路的下调可能有助于糖尿病性ED的发病机制。
