Nishimatsu Hiroaki, Suzuki Etsu, Saito Yasuho, Niimi Aya, Nomiya Akira, Yamada Daisuke, Homma Yukio
The Department of Urology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8512, Japan.
PLoS One. 2015 Jul 24;10(7):e0133874. doi: 10.1371/journal.pone.0133874. eCollection 2015.
Erectile dysfunction (ED) is a major health problem worldwide and affects approximately 75% of diabetic patients, likely due to severely damaged cavernous body. While screening for cytokines produced by adipose tissue-derived stem cells, we detected neuromedin B (NMB). To explore a potential treatment option for ED, we examined whether NMB was capable of restoring erectile function. We also examined the potential mechanism by which NMB could restore erectile function. Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. An adenovirus expressing NMB (AdNMB) was injected into the penis 6 weeks after STZ administration. Four weeks after the injection of AdNMB, erectile function, penile histology, and protein expression were analyzed. As assessed by the measurement of intracavernous pressure, AdNMB injection significantly restored erectile function compared with the injection of an adenovirus expressing green fluorescent protein. This restoration was associated with conservation of the cavernous body structure and neural nitric oxide synthase (nNOS)-expressing nerves, together with recovery of α-smooth muscle actin, vascular endothelial-cadherin, and nNOS expression. Furthermore, NMB significantly stimulated the survival of SH-SY5Y cells derived from human neuroblastoma tissue with characteristics similar to neurons. Collectively, these results suggested that NMB restored erectile function via protection of the cavernous body from injury and stimulation of the survival of the associated nerves. NMB may be useful to treat ED patients with a severely damaged cavernous body.
勃起功能障碍(ED)是全球范围内的一个主要健康问题,大约75%的糖尿病患者受其影响,这可能是由于海绵体严重受损所致。在筛选脂肪组织来源干细胞产生的细胞因子时,我们检测到了神经介素B(NMB)。为了探索ED的一种潜在治疗方法,我们研究了NMB是否能够恢复勃起功能。我们还研究了NMB恢复勃起功能的潜在机制。给雄性Wistar大鼠注射链脲佐菌素(STZ)以诱导糖尿病。在给予STZ 6周后,将表达NMB的腺病毒(AdNMB)注射到阴茎中。注射AdNMB四周后,分析勃起功能、阴茎组织学和蛋白表达。通过测量海绵体内压力评估,与注射表达绿色荧光蛋白的腺病毒相比,注射AdNMB显著恢复了勃起功能。这种恢复与海绵体结构和表达神经型一氧化氮合酶(nNOS)的神经的保留有关,同时α-平滑肌肌动蛋白、血管内皮钙黏蛋白和nNOS表达也得以恢复。此外,NMB显著刺激了源自人神经母细胞瘤组织且具有类似于神经元特征的SH-SY5Y细胞的存活。总体而言,这些结果表明,NMB通过保护海绵体免受损伤和刺激相关神经的存活来恢复勃起功能。NMB可能对治疗海绵体严重受损的ED患者有用。