부산대학교 도서관

Background Sodium butyrate (NaB) is a short-chain fatty acid produced by intestinal microbial fermentation of dietary fiber, and has been shown to be effective in inhibiting ulcerative colitis (UC). However, how NaB regulates inflammation and oxidative stress in the pathogenesis of UC is not clear. Aims The purpose of this study was to use a dextran sulfate sodium salt (DSS)-induced murine colitis model, and determine the effects of NaB and the related molecular mechanisms. Methods Colitis model was induced in mice by administration of 2.5%(wt/vol) DSS. 0.1 M NaB in drinking water, or intraperitoneal injection of NaB (1 g/kg body weight) was given during the study period. In vivo imaging was performed to detect abdominal reactive oxygen species (ROS). Western blotting and RT-PCR were used to determine the levels of target signals. Results The results showed that NaB decreases the severity of colitis as determined by an improved survival rate, colon length, spleen weight, disease activity index (DAI), and histopathological changes. NaB reduced oxidative stress as determined by a reduction in abdominal ROS chemiluminescence signaling, inhibition of the accumulation of myeloperoxidase and malondialdehyde, and restoration of glutathione activity. NaB activated the COX-2/Nrf2/HO-1 pathway by increasing the expressions of COX-2, Nrf2, and HO-1 proteins. NaB inhibited the phosphorylation of NF-[kappa]B and activation of NLRP3 inflammasomes, and reduced the secretion of corresponding inflammatory factors. Furthermore, NaB promoted the occurrence of mitophagy via activating the expression of Pink1/Parkin. Conclusions In conclusion, our results indicate that NaB improves colitis by inhibiting oxidative stress and NF-[kappa]B/NLRP3 activation, which may be via COX-2/Nrf2/HO-1 activation and mitophagy. Graphical Abstract
Author(s): Zhongbo Bian [sup.1], Qiuyu Zhang [sup.1], Yong Qin [sup.1], Xiaodie Sun [sup.1], Lulin Liu [sup.1], Huahuan Liu [sup.1], Lianzhi Mao [sup.1], Yiran Yan [sup.2], Wenzhen Liao [sup.1], Longying Zha [...]