Department of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
J Surg Res. 2013 Nov;185(1):182-9. doi: 10.1016/j.jss.2013.05.013. Epub 2013 May 28.
Resveratrol has been shown to attenuate reactive oxygen species formation and protect against ischemia-reperfusion (I/R) injury. However, the effects of resveratrol against subacute intestinal I/R injury are not clearly elucidated. Therefore, this study was designed to investigate the effects and possible protective mechanisms of resveratrol on subacute intestinal I/R injury in mice.
BALB/c mice were subjected to 1 h ischemia by occluding the superior mesenteric artery and 24 h reperfusion. Histologic injury; myeloperoxidase, superoxide dismutase, and glutathione peroxidase activity; malondialdehyde level; inducible nitric oxide synthase (iNOS), Ac-NF-κBp65, and sirtuin 1 (SIRT1) expression; NF-κB translocation; and nitric oxide (NO) production were examined in treated with or without resveratrol in the absence or presence of pharmacologic inhibitors.
Resveratrol significantly ameliorated subacute intestinal I/R injury accompanied with the decrease of NO production as well as iNOS expression. In addition, resveratrol obviously upregulated the expression of SIRT1 and inhibited the activity of NF-κB. After application of iNOS inhibitor S-methylisothiourea and NF-κB inhibitor pyrrolidine dithiocarbamate, the protective effect of resveratrol was significantly augmented by attenuating iNOS and NO production, indicating that resveratrol exerted its protective effect on intestinal I/R injury via NF-κB-mediated iNOS pathway. Furthermore, the protective effect of resveratrol was correlated with SIRT1, because application of SIRT1 inhibitor nicotinamide strikingly weakened the protective effect of resveratrol.
Taken together, our findings showed that resveratrol protects intestinal subacute I/R injury via the SIRT1-NF-κB pathway in an iNOS-NO-dependent manner. Therefore, resveratrol has a potential clinical prospect for further development of anti-injury therapy.
白藜芦醇已被证明可以减弱活性氧的形成并防止缺血再灌注（I / R）损伤。然而，白藜芦醇对亚急性肠 I / R 损伤的作用尚未阐明。因此，本研究旨在研究白藜芦醇对小鼠亚急性肠 I / R 损伤的作用及其可能的保护机制。
通过阻断肠系膜上动脉 1 小时来使 BALB / c 小鼠发生缺血，然后进行 24 小时再灌注。在存在或不存在药理抑制剂的情况下，用或不用白藜芦醇处理，检查组织学损伤；髓过氧化物酶，超氧化物歧化酶和谷胱甘肽过氧化物酶活性；丙二醛水平；诱导型一氧化氮合酶（iNOS），Ac-NF-κBp65和沉默调节蛋白 1（SIRT1）表达；NF-κB 易位；以及一氧化氮（NO）的产生。
白藜芦醇明显改善了亚急性肠 I / R 损伤，同时减少了 NO 的产生和 iNOS 的表达。此外，白藜芦醇明显上调了 SIRT1 的表达并抑制了 NF-κB 的活性。应用 iNOS 抑制剂 S-甲基异硫脲和 NF-κB 抑制剂吡咯烷二硫代氨基甲酸盐后，通过减轻 iNOS 和 NO 的产生，白藜芦醇的保护作用明显增强，表明白藜芦醇通过 NF-κB 介导的 iNOS 途径发挥对肠 I / R 损伤的保护作用。此外，白藜芦醇的保护作用与 SIRT1 相关，因为应用 SIRT1 抑制剂烟酰胺可显着削弱白藜芦醇的保护作用。
综上所述，我们的研究结果表明，白藜芦醇通过 SIRT1-NF-κB 途径在 iNOS-NO 依赖性方式下保护肠道亚急性 I / R 损伤。因此，白藜芦醇具有进一步开发抗损伤疗法的潜在临床前景。
