Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait.
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
Biomed Pharmacother. 2021 Jun;138:111486. doi: 10.1016/j.biopha.2021.111486. Epub 2021 Mar 30.
Erectile dysfunction (ED) is a common diabetic complication. Recent evidence has illuminated the role of hydrogen sulfide (HS) as a dynamic mediator of the erection process. HS is a potent endogenous relaxant gas. It has been shown to relax human and animal penile tissue in vitro and induce erection in animals in vivo. The reported penile expression of HS-synthesizing enzymes also supports the potential role of the endogenous L-cysteine/HS pathway in penile homeostasis. Several pathological changes take place in the diabetic penile tissue, including inflammation, oxidative stress, neuropathy and fibrosis of the corpus cavernosum (CC), the major erectile structure of the penis. The present study is experimental and has been performed in the diabetic rat model. The study will investigate the role of HS as a potential protective mediator against diabetes-induced structural and functional alterations in the CC by examining if it: (1) reduces corporal contraction and/or enhances corporal relaxation following pharmacological stimulation, (2) attenuates fibromuscular changes in diabetic CC, and (3) whether there is a link with HS plasma/urine level and CC tissue generation, as well as studying the expression of some proteins in the transforming growth factor (TGF)-β1-associated pathway. The major findings of the study reveal that- compared to the nondiabetic controls - the diabetic animals CC showed: (1) augmented contraction and attenuated relaxation in response to phenylephrine and carbachol, respectively, (2) marked fibromuscular degeneration with a significantly lower smooth muscle/collagen ratio and upregulation of TGF-β-1/Smad/CTGF fibrosis signaling pathway, (3) reduced HS plasma and urinary levels and cavernosal tissue generation. Chronic GYY4137 treatment prevented most of these pathological changes in diabetic CC, thus may be considered a potential new strategy for the prevention and/or treatment of diabetes-induced ED.
勃起功能障碍（ED）是一种常见的糖尿病并发症。最近的证据表明，硫化氢（HS）作为勃起过程中的动态介质具有重要作用。HS 是一种有效的内源性松弛气体。它已被证明可在体外松弛人和动物的阴茎组织，并在体内诱导动物勃起。报告的阴茎 HS 合成酶表达也支持内源性 L-半胱氨酸/HS 途径在阴茎稳态中的潜在作用。糖尿病阴茎组织会发生几种病理变化，包括炎症、氧化应激、神经病变和海绵体纤维化（CC），CC 是阴茎的主要勃起结构。本研究是实验性的，在糖尿病大鼠模型中进行。该研究将通过检查 HS 是否：（1）减少药物刺激后海绵体的收缩和/或增强海绵体的松弛，（2）减轻糖尿病 CC 的纤维肌肉变化，以及（3）是否与 HS 血浆/尿液水平和 CC 组织生成有关，以及研究转化生长因子（TGF）-β1 相关途径中的一些蛋白质的表达，来研究 HS 作为一种潜在的保护性介质在对抗 CC 结构和功能改变中的作用。该研究的主要发现表明，与非糖尿病对照组相比，糖尿病动物的 CC 表现出：（1）对苯肾上腺素和卡巴胆碱的反应分别增强收缩和减弱松弛，（2）明显的纤维肌肉退化，平滑肌/胶原比显著降低，TGF-β-1/Smad/CTGF 纤维化信号通路上调，（3）HS 血浆和尿液水平以及海绵体组织生成减少。慢性 GYY4137 治疗可预防糖尿病 CC 中的大多数这些病理变化，因此可能被认为是预防和/或治疗糖尿病性 ED 的一种潜在新策略。
