Differential expression of neurotrophins in penises of streptozotocin-induced diabetic rats
Differential expression of neurotrophins in penises of streptozotocin-induced diabetic rats
复制标题
DOI：
10.2164/jandrol.106.000794
复制
发表时间：
2007-03-01
影响因子：
--
通讯作者：
Dai, Yutian
中科院分区：
文献类型：
--
作者：
Chen, Yun;Yang, Rong;Dai, Yutian
为探讨糖尿病性勃起功能障碍的发病机制，我们研究了神经营养因子在糖尿病大鼠阴茎组织中的分布，包括神经生长因子（NGF）、脑源性神经营养因子（BDNF）、神经营养因子-3（NT-3）和神经营养因子-4（NT-4）。雄性Sprague-Dawley大鼠注射65 mg/kg链脲佐菌素诱导糖尿病（DM）。对照组大鼠作为年龄匹配的对照。8周后，测量电刺激后和处死前大鼠的海绵体间压（ICP）。将每个去皮的阴茎分为2部分，一部分用于免疫组织化学，另一部分用于Western印迹分析。与溶剂对照组大鼠相比，DM组大鼠的ICP显著降低。糖尿病大鼠阴茎组织中NGF阳性神经元明显多于对照组，而BDNF阳性神经元则相反。Western blot结果显示，糖尿病大鼠脑组织中NGF、NT-3、NT-4蛋白表达均增加，而BDNF蛋白表达减少。本研究首次揭示了NT-4蛋白在海绵体组织中的表达。这4种神经营养因子在海绵体组织中的异常水平可能是糖尿病性ED发病的因素之一。神经营养因子的升高可能反映了海绵体组织失神经支配的程度，可能代表了一种代偿机制。高血糖引起的神经逆行轴突运输功能损害可能与此有关。
To explore the mechanism of diabetic erectile dysfunction, we studied the distribution of neurotrophins in the penises of diabetic rats, including nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Male Sprague-Dawley rats were injected with 65 mg/kg streptozotocin to induce diabetes mellitus (DM). The control rats were raised as age-matched control. Eight weeks later, the intercavernous pressure (ICP) of the rats was measured after electrostimulation and before sacrifice. Each peeled penis was divided into 2 parts, one for immunohistochemistry and the other for Western blot analysis. The ICP of the DM group rats was significantly decreased as compared to the vehicle control rats. There were significantly more NGF-positive neurons in the penises of the diabetic rats than in those of the control rats, while the opposite results were observed for BDNF-positive neurons. In the Western blot analysis, the proteins of NGF, NT-3, and NT-4 were all increased, while that of BDNF was decreased in diabetic rats. This is the first study revealing the expression of NT-4 protein in cavernous tissue. The abnormal level of these 4 neurotrophins in cavernous tissue may be one of the factors of the pathogenesis of diabetic ED. The increase of neurotrophins may reflect the degree of cavernous tissue denervation and may represent a compensatory mechanism. The lesion of the retrograde axonal transport of the nerves caused by hyperglycemia may be related to this phenomenon.