中药新药与临床药理2026，Vol.37Issue(4)：677-685,9.DOI:10.19378/j.issn.1003-9783.2026.04.010
左金丸对葡聚糖硫酸钠诱导溃疡性结肠炎小鼠巨噬细胞极化的调控机制
Regulatory Mechanism of Zuojin Pills on Macrophage Polarization in Mice with Dextran Sulfate Sodium-Induced Ulcerative Colitis
摘要
Abstract
Objective To investigate the regulatory mechanism of Zuojin Pills on macrophage polarization in mice with dextran sulfate sodium(DSS)-induced ulcerative colitis(UC).Methods Sixty male BALB/c mice were randomly divided into normal group,model group,low-dose Zuojin Pills group,medium-dose Zuojin Pills group,high-dose Zuojin Pills group,and mesalazine group,with 10 mice in each group.An experimental UC model was established using a"2.5%DSS(days 1-7)→ free drinking water(days 8-14)→ 2.5%DSS(days 15-21)"protocol.From day 8 of modeling,the low-,medium-,and high-dose Zuojin Pills groups were administered 0.75,1.5,and 3 g·kg-1 of Zuojin Pills suspension by gavage,respectively;the mesalazine group received 300 mg·kg-1 mesalazine suspension by gavage;the normal and model groups were given an equal volume of distilled water by gavage,once daily for 14 consecutive days.During modeling,general conditions and body mass of mice were observed daily,and the disease activity index(DAI)was calculated.Colon length,mass,and colon mass index were measured.Histopathological changes in colon tissue were observed by HE staining.Flow cytometry was used to assess M1/M2 polarization and metabolic levels of macrophages in mesenteric lymph nodes.Western Blot was performed to detect the protein expression levels of glucose transporter 1(GLUT1),hexokinase 2(HK2),and pyruvate kinase M2(PKM2)in colon tissue.Results Compared with the normal group,the model group showed significantly decreased body mass(P＜0.01)and significantly increased DAI(P＜0.01);colon length was significantly shortened(P＜0.01),while colon weight and colon mass index were significantly increased(P＜0.01);crypt numbers were reduced with atrophy and deformation,and a large number of lymphocytes,plasma cells,and neutrophils infiltrated the lamina propria,with significantly elevated pathological injury scores(P＜0.01);the expression level of MHC-Ⅱ+in CD11b+F4/80+cells from mesenteric lymph nodes was significantly increased(P＜0.01),while that of CD206+was significantly decreased(P＜0.01);the 2-NBDG ⁺ expression level in CD11b+F4/80+MHC-Ⅱ+cells was significantly increased(P＜0.01),whereas that in CD11b+F4/80+CD206+cells was significantly decreased(P＜0.01);the protein expression levels of GLUT1,HK2,and PKM2 in colon tissue were all significantly increased(P＜0.05,P＜0.01).Compared with the model group,the low-and medium-dose Zuojin Pills groups exhibited significantly increased body mass(P＜0.05,P＜0.01)and significantly decreased DAI(P＜0.05,P＜0.01);all treatment groups showed significantly elongated colon length(P＜0.01)and significantly reduced colon weight and colon mass index(P＜0.05,P＜0.01);the low-and medium-dose Zuojin Pills groups displayed varying degrees of recovery in colonic mucosal damage,significantly reduced inflammatory cell infiltration,relatively regular epithelial cell arrangement,and significantly lower pathological injury scores(P＜0.05,P＜0.01);the medium-and high-dose Zuojin Pills groups showed significantly decreased MHC-Ⅱ+expression in CD11b+F4/80+cells from mesenteric lymph nodes(P＜0.05,P＜0.01),while all Zuojin Pills dose groups exhibited significantly increased CD206+expression in CD11b+F4/80+cells(P＜0.05,P＜0.01);2-NBDG+expression in CD11b+F4/80+MHC-Ⅱ+cells was significantly decreased(P＜0.05,P＜0.01),whereas that in CD11b+F4/80+CD206+cells was significantly increased(P＜0.05,P＜0.01);the medium-dose Zuojin Pills group showed significantly reduced protein expression levels of GLUT1 and HK2 in colon tissue(P＜0.05),and all Zuojin Pills dose groups exhibited significantly decreased PKM2 protein expression in colon tissue(P＜0.05,P＜0.01).Conclusion Zuojin Pills can ameliorate DSS-induced UC in mice by regulating M1/M2 polarization of macrophages,and its mechanism may be related to the inhibition of glycolysis mediated by the GLUT1/HK2/PKM2 signaling pathway.关键词
左金丸/溃疡性结肠炎/巨噬细胞/M1/M2 极化/糖酵解/GLUT1/HK2/PKM2 信号通路/小鼠Key words
Zuojin Pills/ulcerative colitis/macrophages/M1/M2 polarization/glycolysis/GLUT1/HK2/PKM2 signaling pathway/mice分类
医药卫生引用本文复制引用
孙佳钰,汪博,李超,李陈城,曾诚,吕旭涵,王海燕,葛巍..左金丸对葡聚糖硫酸钠诱导溃疡性结肠炎小鼠巨噬细胞极化的调控机制[J].中药新药与临床药理,2026,37(4):677-685,9.基金项目
国家自然科学基金项目(82160870) （82160870）
江西省自然科学基金项目(20224BAB206099) （20224BAB206099）
江西省教育厅科研项目(GJJ2200910) （GJJ2200910）
江西省中医药管理局科技计划项目(2022A340) （2022A340）
江西省中医药中青年骨干人才培养计划项目(赣中医药科教字[2022]7号). （赣中医药科教字[2022]7号）
