Modulation of SIRT1 expression improves erectile function in aged rats.
- Author:
Wen YU
1
;
Jing WANG
1
;
Yu-Tian DAI
1
;
Bin WANG
1
;
Yang XU
1
;
Qing-Qiang GAO
1
;
Zhi-Peng XU
1
Author Information
- Publication Type:Journal Article
- Keywords: SIRT1 expression; apoptosis; erectile function; nitric oxide/cyclic guanosine monophosphate signaling; oxidative stress
- MeSH: Animals; Male; Rats; Cyclic GMP/metabolism*; Erectile Dysfunction/metabolism*; Nitric Oxide/metabolism*; Penile Erection; Penis/pathology*; Phosphodiesterase 5 Inhibitors/pharmacology*; Rats, Sprague-Dawley; Sirtuin 1/metabolism*; Superoxide Dismutase/metabolism*; Tumor Suppressor Protein p53/metabolism*
- From: Asian Journal of Andrology 2022;24(6):666-670
- CountryChina
- Language:English
- Abstract: 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.
