Abstract: Objective To investigate the effect of high-dose red meat diet(H-red)on ulcerative colitis(UC)in mice and the potential mechanism of M1 macrophage polarization promoted by sirtuin 1(Sirt1)/nuclear factor-κB(NF-κB)pathway.Methods Mouse UC model was established with dextran sulfate sodium(DSS)and fed on H-red.Mice were divided into 5 groups:Normal group,UC group,H-red+UC group,resveratrol(RES)treatment group(RES+H-red+UC group),and RES combined with NF-κB inhibitor(quininib,QNZ)treatment group(QNZ+RES+H-red+UC group),10 mice in each group.Body weight,colon length,disease activity index(DAI),myeloperoxidase(MPO)activity were detected.The expression levels of Sirt1/NF-κB signaling pathway proteins and the acetylated NF-κB-p65 in colon tissues were detected by Western blotting.The number of M1 macrophages(F4/80⁺iNOS⁺)was detected by immunofluorescence chemistry,and the mRNA expression levels of inflammatory factors such as IL-6 and TNF-α were detected by qPCR.Results Compared with the UC group,the H-red+UC group had more weight loss,shorter colon length,and further aggravated abnormalities in DAI,pathological changes and MPO activity(all P<0.05),In addition,the Sirt1 expression was inhibited,while acetylated NF-κB-p65 expression,M1 macrophage count and mRNA expression of IL-6,TNF-α,IL-1β,MCP-1,CXCL10 and COX-2 were increased in the H-red+UC group(all P<0.05).Compared with the H-red+UC group,the RES+H-red+UC group showed significant improvement in inflammatory injury,upregulated Sirt1 expression,and significant improvement in the above abnormal indicators(all P<0.05),the QNZ+RES+H-red+UC group had an even better therapeutic effect than the RES+H-red+UC group.Conclusion High red meat diet promotes M1 macrophage polarization and aggravates UC in mice through the Sirt1/NF-κB signaling pathway.

Key words: high-dose red meat diet, ulcerative colitis, Sirt1/NF-κB pathway, M1 macrophage polarization