Shirai Masato, Yamanaka Masaki, Shiina Hiroaki, Igawa Mikio, Kawakami Toshifumi, Ishii Nobuhisa, Lue Tom F, Fujime Makoto, Dahiya Rajvir
Department of Urology, Veterans Affairs Medical Center and University of California at San Francisco, USA.
Biochem Biophys Res Commun. 2006 Mar 17;341(3):755-62. doi: 10.1016/j.bbrc.2005.12.226. Epub 2006 Jan 19.
Previous studies have shown that intracavernous injection of vascular endothelial growth factor (VEGF) restored erectile function in diabetic rats. However, the mechanism of VEGF in diabetes-related erectile dysfunction (ED) has not been fully investigated. We hypothesize that intracavernous injection of VEGF may reverse diabetes-related ED through modulation of the insulin-like growth factor system and sex hormone receptors. To test this hypothesis the erectile function of treated and control rats was analyzed by measurement of intracavernous pressure (ICP) following electrostimulation of the cavernous nerves. Mean ICP was significantly lower in non-treated diabetic rats compared to controls. After VEGF injection, ICP was significantly higher than in non-treated diabetic rats. IGFBP-3 mRNA and protein expression was significantly higher in non-treated diabetic rat crura than controls, while VEGF-treated animals had control levels. ER-beta and PR mRNA and protein expression was significantly lower in non-treated diabetic rat crura. After VEGF injection, ER-beta and PR mRNA and protein expression was similar to control levels. Expression of AR and ER-alpha was the same in all groups. These findings suggest that orthotopic injection of VEGF may improve the functional recovery of diabetes-related ED through modulation of the insulin-like growth factor system and sex hormone receptors. To our knowledge, this is the first study demonstrating that VEGF treatment restores erectile function through restoration of the insulin-like growth factor system and sex hormone receptor genes at the mRNA and protein levels in diabetic rat crura. These results may be important in understanding the pathogenesis of diabetes-related ED and also in providing better strategies for management of this disease.
先前的研究表明，海绵体内注射血管内皮生长因子（VEGF）可恢复糖尿病大鼠的勃起功能。然而，VEGF在糖尿病相关性勃起功能障碍（ED）中的作用机制尚未得到充分研究。我们推测，海绵体内注射VEGF可能通过调节胰岛素样生长因子系统和性激素受体来逆转糖尿病相关性ED。为了验证这一假设，通过测量海绵体神经电刺激后的海绵体内压（ICP）来分析治疗组和对照组大鼠的勃起功能。与对照组相比，未治疗的糖尿病大鼠的平均ICP显著降低。注射VEGF后，ICP显著高于未治疗的糖尿病大鼠。未治疗的糖尿病大鼠海绵体白膜中IGFBP-3 mRNA和蛋白表达显著高于对照组，而VEGF治疗的动物则达到对照水平。未治疗的糖尿病大鼠海绵体白膜中ER-β和PR mRNA及蛋白表达显著降低。注射VEGF后，ER-β和PR mRNA及蛋白表达与对照水平相似。所有组中AR和ER-α的表达相同。这些发现表明，原位注射VEGF可能通过调节胰岛素样生长因子系统和性激素受体来改善糖尿病相关性ED的功能恢复。据我们所知，这是第一项证明VEGF治疗通过在糖尿病大鼠海绵体白膜的mRNA和蛋白水平上恢复胰岛素样生长因子系统和性激素受体基因来恢复勃起功能的研究。这些结果对于理解糖尿病相关性ED的发病机制以及为该疾病提供更好的治疗策略可能具有重要意义。
