中国病理生理杂志2025,Vol.41Issue(6):1181-1189,9.DOI:10.3969/j.issn.1000-4718.2025.06.015
湖北枫杨总黄酮通过调节巨噬细胞极化减轻DSS诱导的小鼠溃疡性结肠炎
Total flavonoids of Pterocarya hupehensis Skan alleviate DSS-induced ul-cerative colitis in mice by modulating macrophage polarization
摘要
Abstract
AIM:To investigate the effects of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on dex-tran sulfate sodium(DSS)-induced ulcerative colitis(UC)mouse model and lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages.METHODS:Thirty-six male C57BL/6J mice(6 to 8 weeks old,SPF grade)were randomly di-vided into 6 groups:negative control(NC)group,3%DSS-induced model group,mesalazine(300 mg·kg-1·d-1)group,and low-dose(62.5 mg·kg-1·d-1),medium-dose(125 mg·kg-1·d-1)and high-dose(250 mg·kg-1·d-1)PHSTF treatment groups,with 6 mice in each group.The mice in NC group received distilled water,while those in other groups were treated with a 3%DSS solution for 7 d to induce the UC model.On the 1st day of DSS administration,the mice in treatment groups received the corresponding agents via oral gavage for 10 d,while those in NC and model groups were gavaged with distilled water.Throughout the study,the effects of PHSTF on body weight,fecal blood,and colon length were measured and recorded daily.Histopathological changes in colon tissues were assessed using hematoxylin-eosin staining.The levels of the pro-inflammatory cytokine interleukin-1β(IL-1β)and the anti-inflammatory cytokine IL-10 in colon tissues were quantified using ELISA.The LPS-induced RAW264.7 macrophage model was employed to evaluate the cellular effects of PHSTF.Cell viability was assessed by CCK-8 assay,and cell morphology was observed under a microscope.The mRNA expression of inflammatory markers[IL-1β,inducible nitric oxide synthase(iNOS),IL-10 and arginase-1(Arg-1)]was measured by RT-qPCR.Western blot and immunofluorescence double labeling were used to detect the protein expression of macrophage polarization markers(iNOS,CD206 and Arg-1).Finally,immunohistochemistry(IHC)was utilized to as-sess protein expression of iNOS in colon tissues.RESULTS:Compared to the DSS-induced UC model group,PHSTF sig-nificantly improved several parameters,including weight loss(P<0.05),rectal bleeding,and colon shortening in DSS-treated mice.PHSTF also reduced histopathological damage and inflammatory cell infiltration in the colon.It decreased IL-1β levels(P<0.05)and increased IL-10 levels(P<0.05)in colon tissues.In LPS-induced RAW264.7 cells,PHSTF reduced the mRNA expression of IL-1β and iNOS(P<0.01),while upregulating the mRNA expression of IL-10 and Arg-1(P<0.01).Additionally,PHSTF decreased iNOS protein expression(P<0.01)and elevated the expression of Arg-1 and CD206 proteins(P<0.01).IHC analysis further confirmed that PHSTF downregulated iNOS protein expression in colon tissues.CONCLUSION:Treatment with PHSTF promotes the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,thereby alleviating inflammation in colon tissue and ameliorating ulcer-ative colitis in mice.关键词
湖北枫杨总黄酮/溃疡性结肠炎/巨噬细胞极化Key words
total flavonoids of Pterocarya hupehensis Skan/ulcerative colitis/macrophage polarization分类
医药卫生引用本文复制引用
陈国庆,沈秀兰,刘晓镕,金金,闫冬,刘人嘉,向珊,袁林,向阳,吴昊..湖北枫杨总黄酮通过调节巨噬细胞极化减轻DSS诱导的小鼠溃疡性结肠炎[J].中国病理生理杂志,2025,41(6):1181-1189,9.基金项目
国家自然科学基金资助项目(No.81960776) (No.81960776)
湖北省自然科学基金联合基金项目(No.2023AFD069) (No.2023AFD069)
恩施土家族苗族自治州科技局技术支撑项目(No.D20230022) (No.D20230022)
恩施市恩施州土家苗族自治州科技局科技项目(No.E20240006) (No.E20240006)
湖北恩施学院校级科研一般项目(No.KYZX202402) (No.KYZX202402)