Institute of Andrology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210000, China.
Asian J Androl. 2022 Nov-Dec;24(6):666-670. doi: 10.4103/aja202199.
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), niacinamide (NAM; 500 mg kg) or Res (5 mg kg) + tadalafil (Tad; phosphodiesterase-5 [PDE5] inhibitor; 5 mg kg) 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.
沉默信息调节因子 2 相关酶 1（SIRT1）是一种与衰老相关的蛋白，随着衰老而被激活。在此，我们评估了 SIRT1 在与衰老相关的勃起功能障碍中的作用。通过灌胃给予白藜芦醇（Res；5mg/kg）、烟酰胺（NAM；500mg/kg）或 Res（5mg/kg）+他达拉非（Tad；磷酸二酯酶-5 [PDE5]抑制剂；5mg/kg）8 周，调节老年 Sprague-Dawley 大鼠的 SIRT1 表达。然后，通过测量海绵体内压（ICP）/平均系统动脉压（MAP）的比值来确定勃起功能。提取海绵体组织，通过免疫组织化学、末端脱氧核苷酸转移酶（TdT）介导的 2'-脱氧尿苷 5'-三磷酸（dUTP）缺口末端标记（TUNEL）、酶联免疫吸附测定和 Western blot 分析，评估组织学变化、细胞凋亡、一氧化氮（NO）/环磷酸鸟苷（cGMP）、超氧化物歧化酶（SOD）/3,4-亚甲基二氧基苯丙胺（MDA）水平以及 SIRT1、p53 和叉头框 O3（FOXO3a）的表达。与对照组相比，Res 治疗可显著改善勃起功能，表现为平滑肌和内皮细胞含量增加、NO/cGMP 和 SOD 活性增加、细胞凋亡和 MDA 水平降低。加入 Tad 可提高 Res 的作用。此外，Res 组 SIRT1 蛋白表达增加，p53 和 FOXO3a 水平降低。此外，通过 NAM 处理抑制 SIRT1 会导致与 Res 处理相比的不良反应。SIRT1 激活可改善与衰老相关的勃起功能障碍，支持 SIRT1 作为勃起功能障碍治疗靶点的潜力。
