中文摘要：

AIM To investigate the role of the mi R-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease(IBD)and to explore the potential downstream mechanisms with respect to inflammation,oxidative stress and energy metabolism.METHODS C57BL/6 mice were fed dextran sulfate sodium(DSS)liquid for 7 consecutive days,followed by the administration of saline to the DSS group,UCP2 si RNA to the UCP2 group and a mi R-133a mimic to the mi R-133a group on days 8 and 11.Body weight,stool consistencyand rectal bleeding were recorded daily,and these composed the disease activity index(DAI)score for the assessment of disease severity.After cervical dislocation was performed on day 14,the length of the colon in each mouse was measured,and colonic tissue was collected for further study,which included the following:haematoxylin and eosin staining,UCP2 and mi R-133a detection by immunohistochemical staining,western blot and quantitative real-time PCR,measurement of apoptosis by TUNEL assay,and the assessment of inflammation(TNF-α,IL-1β,IL-6 and MCP1),oxidative stress(H2O2 and MDA)and metabolic parameters(ATP)by ELISA and colorimetric methods.RESULTS An animal model of IBD was successfully established,as shown by an increased DAI score,shortened colon length and specific pathologic changes,along with significantly increased UCP2 and decreased mi R-133a levels.Compared with the DSS group,the severity of IBD was alleviated in the UCP2 and the mi R-133a groups after successful UCP2 knockdown and mi R-133a overexpression.The extent of apoptosis,as well as the levels of TNF-α,IL-1β,MDA and ATP,were significantly increased in both the UCP2 and mi R-133a groups compared with the DSS group.CONCLUSION The mi R-133a-UCP2 pathway participates in IBD by altering downstream inflammation,oxidative stress and markers of energy metabolism,which provides novel clues and potential therapeutic targets for IBD.

英文摘要：

AIM To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and energy metabolism. METHODS C57BL/6 mice were fed dextran sulfate sodium (DSS) liquid for 7 consecutive days, followed by the administration of saline to the DSS group, UCP2 siRNA to the UCP2 group and a miR-133a mimic to the miR-133a group on days 8 and 11. Body weight, stool consistency and rectal bleeding were recorded daily, and these composed the disease activity index (DAI) score for the assessment of disease severity. After cervical dislocation was performed on day 14, the length of the colon in each mouse was measured, and colonic tissue was collected for further study, which included the following: haematoxylin and eosin staining, UCP2 and miR-133a detection by immunohistochemical staining, western blot and quantitative real-time PCR, measurement of apoptosis by TUNEL assay, and the assessment of inflammation (TNF-alpha, IL-1 beta, IL-6 and MCP1), oxidative stress (H2O2 and MDA) and metabolic parameters (ATP) by ELISA and colorimetric methods. RESULTS An animal model of IBD was successfully established, as shown by an increased DAI score, shortened colon length and specific pathologic changes, along with significantly increased UCP2 and decreased miR-133a levels. Compared with the DSS group, the severity of IBD was alleviated in the UCP2 and the miR-133a groups after successful UCP2 knockdown and miR-133a overexpression. The extent of apoptosis, as well as the levels of TNF-alpha, IL-1 beta, MDA and ATP, were significantly increased in both the UCP2 and miR-133a groups compared with the DSS group. CONCLUSION The miR-133a-UCP2 pathway participates in IBD by altering downstream inflammation, oxidative stress and markers of energy metabolism, which provides novel clues and potential therapeutic targets for IBD.