浙江医学2025，Vol.47Issue(17)：1799-1805,后插1,8.DOI:10.12056/j.issn.1006-2785.2025.47.17.2025-485
基于蛋白质组学探讨小檗碱治疗溃疡性结肠炎的作用机制
Proteomics-based study on the mechanism of action of berberine in improving ulcerative colitis
摘要
Abstract
Objective To investigate the protective effect of berberine on dextran sulphate sodium salt(DSS)-induced ulcerative colitis(UC)in Balb/c mice and to analyze its molecular mechanism using proteomics technology.Methods Twenty-four male Balb/c mice were randomly divided into a control group,a UC model group,and a berberine intervention group.The UC model was established by administering a 3％DSS solution,and the berberine intervention group received daily oral administration of 40 mg/kg berberine.Mice in each group were treated after intervention for 7 d.The disease activity index(DAI)was used to assess the severity of colitis.Serum inflammatory factors,including tumour necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β,as well as oxidative stress markers,including superoxide dismutase(SOD),malondialdehyde(MDA),and catalase(CAT)were detected.Colon permeability was assessed using fluorescein isothiocyanate-dextran to evaluate the efficacy of berberine.Proteomics technology was used to screen for differentially expressed proteins in colon tissue,and RT-qPCR and Western blotting were employed to validate the expression of key genes and proteins.Results Berberine significantly alleviated pathological damage in DSS-induced UC mice.Compared with the UC model group,the weight loss trend in the berberine intervention group was significantly improved,and the DAI score was significantly reduced.Berberine effectively inhibited the elevation of serum pro-inflammatory factors TNF-α,IL-6,and IL-1β,and reversed the activity of SOD,MDA,and CAT.Additionally,berberine significantly repaired intestinal epithelial barrier function by upregulating the expression of tight junction proteins Occludin and Zo-1,and reduced intestinal permeability.Proteomics analysis revealed that 142 differentially expressed proteins(77 up-regulated and 65 down-regulated)were identified in colon tissue after berberine intervention,and the peroxisome proliferator-activated receptor γ(PPARγ)signaling pathway was significantly activated.RT-qPCR and Western blot experiments indicated that berberine could regulate the metabolism-inflammation network by upregulating the expressions of CPT1,FATP2,PPARγ mRNA,and protein,thereby improving UC.Conclusion Berberine improves DSS-induced UC in mice through multiple mechanisms,including the inhibition of systemic inflammatory responses,alleviation of oxidative stress damage,repair of intestinal epithelial barrier integrity,and activation of the PPARγ signaling pathway.关键词
小檗碱/溃疡性结肠炎/蛋白质组学Key words
Berberine/Ulcerative colitis/Proteomics引用本文复制引用
华宏军,徐可珍,杨超,张芸芸,王晓波,叶旭星..基于蛋白质组学探讨小檗碱治疗溃疡性结肠炎的作用机制[J].浙江医学,2025,47(17):1799-1805,后插1,8.基金项目
浙江省基础公益研究计划项目(LGD19H030002) （LGD19H030002）
