末端脱氧核苷酸转移酶
标记法
环磷酸鸟苷
勃起功能障碍
内分泌学
cGMP特异性磷酸二酯酶5型
内科学
细胞凋亡
他达拉非
超氧化物歧化酶
西妥因1
一氧化氮
医学
化学
免疫组织化学
男科
氧化应激
生物化学
下调和上调
基因
作者
Zhipeng Xu,Wen Yao,Jing Wang,Yutian Dai,Bin Wang,Yang Xu,Qiang Gao
摘要
Silent information regulator 2-related enzyme 1 (SIRT1) is an aging-related protein activated with aging. Herein, we evaluated the role of SIRT1 in aging-related erectile dysfunction. The expression of SIRT1 was modulated in aged Sprague-Dawley rats following intragastric administration of resveratrol (Res; 5 mg kg−1), niacinamide (NAM; 500 mg kg−1) or Res (5 mg kg−1) + tadalafil (Tad; phosphodiesterase-5 [PDE5] inhibitor; 5 mg kg−1) for 8 weeks. Then, we determined erectile function by the ratio of intracavernosal pressure (ICP)/mean systemic arterial pressure (MAP). Cavernosal tissues were extracted to evaluate histological changes, cell apoptosis, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP), the superoxide dismutase (SOD)/3,4-methylenedioxyamphetamine (MDA) level, and the expression of SIRT1, p53, and forkhead box O3 (FOXO3a) using immunohistochemistry, terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling (TUNEL), enzyme-linked immunosorbent assays, and western blot analysis. Compared with the control, Res treatment significantly improved erectile function, reflected by an increased content of smooth muscle and endothelium, NO/cGMP and SOD activity, and reduced cell apoptosis and MDA levels. The effect of Res was improved by adding Tad. In addition, the protein expression of SIRT1 was increased in the Res group, accompanied by decreased p53 and FOXO3a levels. In addition, inhibition of SIRT1 by NAM treatment resulted in adverse results compared with Res treatment. SIRT1 activation ameliorated aging-related erectile dysfunction, supporting the potential of SIRT1 as a target for erectile dysfunction treatment.
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