Zhou Feng, Li Guang-Yong, Gao Zhe-Zhu, Liu Jing, Liu Tao, Li Wei-Ren, Cui Wan-Shou, Bai Guang-Yi, Xin Zhong-Cheng
Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
J Androl. 2012 Jul-Aug;33(4):651-9. doi: 10.2164/jandrol.111.014456. Epub 2011 Oct 20.
Diabetes-associated erectile dysfunction is associated with increased extracellular matrix deposition and reduced smooth muscle content in the corpus cavernosum. The mechanisms of these processes are not well understood. In this study, we investigated fibromuscular changes in the corpus cavernosum of rats with streptozotocin-induced diabetes to determine the mechanisms underlying pathologic changes in penile structure and function. Forty 8-week-old Sprague-Dawley rats were randomly distributed into control and diabetic groups. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin 60 mg/kg. Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real-time intracorporal pressure assessment. The penis was harvested for histologic examination (Masson trichrome stain, picrosirius red stain, Hart elastin stain, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, and immunohistochemistry) and Western blot. Diabetes significantly attenuated erectile response to cavernous nerve electrostimulation. Diabetic animals exhibited a decreased smooth muscle/collagen ratio in the corpus cavernosum. The ratio of collagen I to II fibers was significantly lower in the corpora of diabetic rats compared with controls. Cavernous elastic fibers were fragmented in diabetic rats. There was up-regulation of the transforming growth factor β1/Smad/connective tissue growth factor signaling pathway in diabetic rats. Phospho-Smad2 expression was higher in smooth muscle cells and fibroblasts of diabetic rats, as was the apoptotic index. The up-regulation of the transforming growth factor β1/Smad/connective tissue growth factor signaling pathway might play an important role in diabetes-induced fibrous-muscular structural changes and deterioration of erectile function.
糖尿病相关性勃起功能障碍与海绵体中细胞外基质沉积增加和平滑肌含量减少有关。这些过程的机制尚未完全了解。在本研究中，我们调查了链脲佐菌素诱导的糖尿病大鼠海绵体中的纤维肌肉变化，以确定阴茎结构和功能病理变化的潜在机制。40只8周龄的Sprague-Dawley大鼠随机分为对照组和糖尿病组。通过一次性腹腔注射60mg/kg链脲佐菌素诱导糖尿病。12周后，通过海绵体神经电刺激并实时评估体内压力来测量勃起功能。采集阴茎进行组织学检查（Masson三色染色、苦味酸天狼星红染色、哈特弹性蛋白染色、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记和免疫组织化学）以及蛋白质印迹分析。糖尿病显著减弱了对海绵体神经电刺激的勃起反应。糖尿病动物海绵体中的平滑肌/胶原蛋白比例降低。与对照组相比，糖尿病大鼠阴茎海绵体中I型与II型胶原纤维的比例显著降低。糖尿病大鼠的海绵体弹性纤维断裂。糖尿病大鼠中转化生长因子β1/Smad/结缔组织生长因子信号通路上调。磷酸化Smad2在糖尿病大鼠的平滑肌细胞和成纤维细胞中的表达较高，凋亡指数也是如此。转化生长因子β1/Smad/结缔组织生长因子信号通路的上调可能在糖尿病诱导的纤维肌肉结构变化和勃起功能恶化中起重要作用。
