Cui K, Li R, Chen R, Li M, Wang T, Yang J, Chen Z, Wang S, Liu J, Rao K
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Andrologia. 2018 Feb;50(1). doi: 10.1111/and.12797. Epub 2017 Mar 10.
The aim of this study was to investigate the underlying mechanism of androgen deficiency inducing corporal fibrosis, thereby causing erectile dysfunction (ED). Forty 12-week-old healthy male rats were divided randomly into four groups: normal control group (Control); castration group (Castration); the other 20 rats were castrated followed by testosterone (T) (orally) each day: castration + 10mg/kg T group (Castration + 10T) and castration + 20 mg/kg T group (Castration + 20T). After 8 weeks' treatment, the main outcome measures were the following: serum levels of T; the ratios of intracavernous pressure (ICP) to mean arterial pressure (MAP); histologic changes in penile smooth muscle cells; the Smad and non-Smad pathways; and extracellular matrix (ECM) protein deposition. Castration group showed lower level of T and ratio of ICP/MAP, reduced ratio of penile smooth muscle cells/collagen, increased extracellular matrix protein deposition, and a higher expression of the Smad and non-Smad pathways. Castration + 10T partially preserved erectile function and histology stabilisation. However, the Castration + 20T group showed significantly better erectile function and molecular changes. Better efficacy could be expected with ART of adequate dose. Androgen deficiency induces corporal fibrosis through activation of the Smad and non-Smad pathways, and accumulation of ECM proteins.
本研究旨在探讨雄激素缺乏诱导海绵体纤维化从而导致勃起功能障碍(ED)的潜在机制。将40只12周龄的健康雄性大鼠随机分为四组:正常对照组(Control);去势组(Castration);另外20只大鼠去势后每天给予睾酮(T)(口服):去势 + 10mg/kg T组(Castration + 10T)和去势 + 20mg/kg T组(Castration + 20T)。治疗8周后,主要观察指标如下:血清T水平;海绵体内压(ICP)与平均动脉压(MAP)的比值;阴茎平滑肌细胞的组织学变化;Smad和非Smad信号通路;以及细胞外基质(ECM)蛋白沉积。去势组显示T水平和ICP/MAP比值较低,阴茎平滑肌细胞/胶原蛋白比值降低,细胞外基质蛋白沉积增加,以及Smad和非Smad信号通路的表达较高。去势 + 10T组部分保留了勃起功能和组织学稳定性。然而,去势 + 20T组显示出明显更好的勃起功能和分子变化。适当剂量的雄激素替代疗法有望获得更好的疗效。雄激素缺乏通过激活Smad和非Smad信号通路以及ECM蛋白的积累诱导海绵体纤维化。