- 作者：WenPeng Dong ; FanFan Li ; ZhiGuo Pan ; ShenXi Liu ; Hao Yu ; XianYue Wang ; ShengHui Bi ; WeiDa Zhang
- 关键词：Intestinal ischemia-reperfusion injury ; Resveratrol ; Nitric oxide ; SIRT1 ; NF-魏B
- 刊名：Journal of Surgical Research
- 出版年：November, 2013
- 年：2013
- 卷：185
- 期：1
- 页码：182-189
- 全文大小：1157 K
Background
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.Methods
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-魏Bp65, and sirtuin 1 (SIRT1) expression; NF-魏B translocation; and nitric oxide (NO) production were examined in treated with or without resveratrol in the absence or presence of pharmacologic inhibitors.
Results
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-魏B. After application of iNOS inhibitor S-methylisothiourea and NF-魏B 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-魏B-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.
Conclusions
Taken together, our findings showed that resveratrol protects intestinal subacute I/R injury via the SIRT1-NF-魏B pathway in an iNOS-NO-dependent manner. Therefore, resveratrol has a potential clinical prospect for further development of anti-injury therapy.