高红肉饮食通过Sirt1/NF-κB通路促进M1巨噬细胞极化加重小鼠溃疡性结肠炎

doi:10.3870/j.issn.1672-8009.2026.02.009

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (2): 171-178.doi: 10.3870/j.issn.1672-8009.2026.02.009

高红肉饮食通过Sirt1/NF-κB通路促进M1巨噬细胞极化加重小鼠溃疡性结肠炎

刘芳¹, 郑森元², 李丹萍¹

¹新疆医科大学第五附属医院全科医学科乌鲁木齐市,830011
²新疆医科大学第一附属医院消化二科乌鲁木齐市,830054

收稿日期:2025-04-18 出版日期:2026-03-31 发布日期:2026-04-03
通讯作者: 李丹萍(E-mail:635323650@qq.com)
基金资助:
新疆维吾尔族自治区自然科学基金(No.2022D01C321)

High-Dose Red Meat Diet Promotes M1-Macrophage Polarization and Aggravates Ulcerative Colitis in Mice by Sirt1/NF-κB Pathway

LIU Fang¹, ZHENG Senyuan², LI Danping¹

¹Department of General Medicine,The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi,830011,China
²Department of Gastroenterology,First Affiliated Hospital of Xinjiang Medical University,Urumqi,830054,China

Received:2025-04-18 Online:2026-03-31 Published:2026-04-03
Contact: LI Danping(E-mail:635323650@qq.com)
Supported by:
Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2022D01C321)

摘要/Abstract

摘要： 目的探讨高比例红肉饮食(high-dose red meat diet,H-red)对小鼠溃疡性结肠炎(ulcerative colitis,UC)的影响及基于沉默信息调节因子2类蛋白1(sirtuin 1,Sirt1)/核因子-κB(nuclear factor-κB,NF-κB)通路促进M1巨噬细胞极化的潜在机制。方法采用葡聚糖硫酸钠建立小鼠UC模型并给予H-red喂养,将小鼠分为健康组(Normal组)、UC组、H-red+UC组、白藜芦醇(resveratrol,RES)治疗组(RES+H-red+UC组)、RES和NF-κB抑制剂(quininib,QNZ)联合治疗组(QNZ+RES+H-red+UC组),每组10只。检测各组小鼠体质量、结肠长度、疾病活动度,髓过氧化物酶(myeloperoxidase,MPO)活性,通过蛋白质印迹法检测结肠组织Sirt1/NF-κB信号通路蛋白及乙酰化NF-κB-p65表达,免疫荧光化学法检测M1型巨噬细胞(F4/80⁺iNOS⁺)数量,qPCR法检测IL-6、TNF-α等炎症因子mRNA表达。结果与UC组相比,H-red+UC组小鼠的体重减轻、结肠长度更短,疾病活动指数、病理变化和MPO活性异常进一步加重(P_均＜0.05);且Sirt1表达受抑制,乙酰化NF-κB-p65表达、M1巨噬细胞数量及IL-6、TNF-α、IL-1β、MCP-1、CXCL10、COX-2 mRNA表达均升高(P_均＜0.05)。与H-red+UC组相比,RES+H-red+UC组炎症损伤明显改善,Sirt1表达上调,上述异常指标均显著改善(P_均＜0.05);QNZ+RES+H-red+UC组治疗效果更显著。结论高红肉饮食通过Sirt1/NF-κB信号通路促进M1巨噬细胞极化,加重小鼠溃疡性结肠炎。

关键词: 高比例红肉饮食, 溃疡性结肠炎, Sirt1/NF-κB通路, M1巨噬细胞极化

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

中图分类号:

R574.62

刘芳, 郑森元, 李丹萍. 高红肉饮食通过Sirt1/NF-κB通路促进M1巨噬细胞极化加重小鼠溃疡性结肠炎[J]. 医学分子生物学杂志, 2026, 23(2): 171-178.

LIU Fang, ZHENG Senyuan, LI Danping. High-Dose Red Meat Diet Promotes M1-Macrophage Polarization and Aggravates Ulcerative Colitis in Mice by Sirt1/NF-κB Pathway[J]. Journal of Medical Molecular Biology, 2026, 23(2): 171-178.

参考文献

[1] ABU-GHAZALEH N,CHUA W J,GOPALAN V.Intestinal microbiota and its association with colon cancer and red/processed meat consumption[J].J Gastroenterol Hepatol,2021,36(1):75-88.
[2] LI D P,CUI M,TAN F,et al.High red meat intake exacerbates dextran sulfate-induced colitis by altering gut microbiota in mice[J].Front Nutr,2021,8:646819.
[3] KATSANDEGWAZA B,HORSNELL W,SMITH K.Inflammatory bowel disease:A review of pre-clinical murine models of human disease[J].Int J Mol Sci,2022,23(16):9344.
[4] CAO L,TAN Q,ZHU R,et al.LncRNA MIR4435-2 HG suppression regulates macrophage M1/M2 polarization and reduces intestinal inflammation in mice with ulcerative colitis[J].Cytokine,2023,170:156338.
[5] LI Y,XI Y,TAO G,et al.Sirtuin 1 activation alleviates primary biliary cholangitis via the blocking of the NF-κB signaling pathway[J].Int Immunopharmacol,2020,83:106386.
[6] ZHANG J,LIN B,ZHANG Y,et al.Baitouweng decoction alleviates ulcerative colitis by regulating tryptophan metabolism through DOPA decarboxylase promotion[J].Front Pharmacol,2024,15:1423307.
[7] YAO J,WEI C,WANG J Y,et al.Effect of resveratrol on Treg/Th17 signaling and ulcerative colitis treatment in mice[J].World J Gastroenterol,2015,21(21):6572-6581.
[8] ZHANG G,YANG F,LI J,et al.A quinazoline derivative suppresses B cell hyper-activation and ameliorates the severity of systemic lupus erythematosus in mice[J].Front Pharmacol,2023,14:1159075.
[9] 陈岩勤,李燕,杨盛刚,等.姜黄素对小鼠溃疡性结肠炎疗效及免疫作用机制[J].中国老年学杂志,2023,43(10):2468-2472.
CHEN Y L,LI Y,YANG S G,et al.Therapeutic effect and immune mechanism on ulcerative colitis treated by curcumin in mice[J].Chin J Gerontol,2023,43(10):2468-2472.
[10] 王宇,黄益娜,蔡昀洁,等.约氏乳杆菌GLJO02通过改善肠道通透性缓解DSS诱导的小鼠结肠炎[J].中国微生态学杂志,2023,35(3):284-290.
WANG Y,HUANG Y N,CAI Y J,et al.Lactobacillus johnsonii GLJO02 alleviates DSS-induced colitis inmice by improving intestinal permeability[J].Chin J Microecol,2023,35(3):284-290.
[11] JIA X,GAO Y,LIU L,et al.Artemisinin alleviates intestinal inflammation and metabolic disturbance in ulcerative colitis rats induced by DSS[J].Evid Based Complement Alternat Med,2022,2022:6211215.
[12] CHEN R,LIN X,WANG Q,et al.Dual-targeting celecoxib nanoparticles protect intestinal epithelium and regulate macrophage polarization for ulcerative colitis treatment[J].Chem Eng J,2023,452:139445.
[13] FENG X,XIE Q,XU H,et al.Yeast microcapsule mediated natural products delivery for treating ulcerative colitis through anti-inflammatory and regulation of macrophage polarization[J].ACS Appl Mater Interfaces,2022,14(27):31085-31098.
[14] LIU L,GUO H,SONG A,et al.Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways[J].BMC Immunol,2020,21(1):32.
[15] SUN J,ZHAO P,DING X,et al.Cayratia japonica prevents ulcerative colitis by promoting M2 macrophage polarization through blocking the TLR4/MAPK/NF-κB pathway[J].Mediators Inflamm,2022,2022:1108569.
[16] GUO C,ZHANG Y,LING T,et al.Chitosan oligosaccharides alleviate colitis by regulating intestinal microbiota and PPARγ/SIRT1-mediated NF-κB pathway[J].Mar Drugs,2022,20(2):96.
[17] GAO T,CHEN S,HAN Y,et al.Ameliorating inflammation in insulin-resistant rat adipose tissue with abdominal massage regulates SIRT1/NF-κB signaling[J].Cell Biochem Biophys,2022,80(3):579-589.

高红肉饮食通过Sirt1/NF-κB通路促进M1巨噬细胞极化加重小鼠溃疡性结肠炎

High-Dose Red Meat Diet Promotes M1-Macrophage Polarization and Aggravates Ulcerative Colitis in Mice by Sirt1/NF-κB Pathway

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