目的 探讨左金丸对葡聚糖硫酸钠（DSS）诱导溃疡性结肠炎（UC）小鼠巨噬细胞极化的调控机制。 方法 将 60 只 BALB/c 雄性小鼠随机分为正常组、模型组、左金丸低剂量组、左金丸中剂量组、左金丸高剂 量组及美沙拉嗪组，每组 10 只。采用“2.5%DSS（第 1～7 天）→自由饮水（第 8～14 天）→2.5% DSS（第 15～21 天）” 的方法复制实验性 UC 小鼠模型。造模第 8 天起，左金丸低、中、高剂量组分别给予 0.75、1.5、3 g·kg-1左金 丸混悬液灌胃；美沙拉嗪组给予 300 mg·kg-1美沙拉嗪混悬液灌胃；正常组、模型组给予等体积蒸馏水灌胃， 每日 1 次，连续 14 d。造模期间，每日观察小鼠一般情况，记录体质量，计算疾病活动指数；测定结肠长度、 质量及结肠质量指数；采用 HE 染色法观察结肠组织病理变化；流式细胞术测定肠系膜淋巴结中巨噬细胞 M1/ M2 极化及代谢水平；Western Blot 法检测结肠组织中葡萄糖转运蛋白 1（GLUT1）、己糖激酶 2（HK2）、丙酮酸 激酶 M2（PKM2）蛋白表达水平。结果 与正常组比较，模型组小鼠的体质量显著降低（P＜0.01），疾病活动指 数显著升高（P＜0.01）；结肠长度显著缩短（P＜0.01），结肠质量及质量指数显著升高（P＜0.01）；隐窝数量减 少、萎缩变形，黏膜固有层中可见大量淋巴细胞、浆细胞和中性粒细胞浸润，病理损伤评分显著升高（P＜ 0.01）；肠系膜淋巴结 CD11b+ F4/80+ 细胞中 MHC-Ⅱ+ 表达水平显著升高（P＜0.01），而 CD206+ 表达水平显著下降 （P＜0.01），CD11b+ F4/80+ MHC-Ⅱ+ 细胞中 2-NBDG+ 表达水平显著升高（P＜0.01），CD11b+ F4/80+ CD206+ 细胞中 2-NBDG+ 表达水平显著降低（P＜0.01）；结肠组织 GLUT1、HK2、PKM2 蛋白表达量均显著升高（P＜0.05，P＜ 0.01）。与模型组比较，左金丸低、中剂量组小鼠的体质量显著升高（P＜0.05，P＜0.01），疾病活动指数显著降 低（P＜0.05，P＜0.01）；各给药组小鼠的结肠长度显著延长（P＜0.01），结肠质量及质量指数显著降低（P＜ 0.05，P＜0.01）；左金丸低、中剂量组小鼠结肠黏膜损伤有不同程度恢复，炎性细胞浸润明显减少，上皮细胞 排列较整齐，病理损伤评分显著降低（P＜0.05，P＜0.01）；左金丸中、高剂量组小鼠肠系膜淋巴结 CD11b+ F4/80+ 细胞中 MHC-Ⅱ+ 表达水平显著下降（P＜0.05，P＜0.01），左金丸各剂量组小鼠肠系膜淋巴结 CD11b+ F4/80+ 细胞 中 CD206+ 表达水平均显著升高（P＜0.05，P＜0.01），CD11b+ F4/80+ MHC-Ⅱ+ 细胞中 2-NBDG+ 表达水平显著下降 （P＜0.05，P＜0.01），CD11b+ F4/80+ CD206+ 细胞中 2-NBDG+ 表达水平显著升高（P＜0.05，P＜0.01）；左金丸中 剂量组小鼠结肠组织 GLUT1、HK2 蛋白表达水平明显降低（P＜0.05），左金丸各剂量组小鼠结肠组织 PKM2 蛋 白表达水平均显著降低（P＜0.05，P＜0.01）。结论 左金丸可通过调节巨噬细胞 M1/M2 极化发挥对 DSS 诱导 UC 小鼠的改善作用，其作用机制可能与 GLUT1/HK2/PKM2 信号通路介导的糖酵解被抑制有关。

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 mediumdose 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.

R285.5

国家自然科学基金项目（82160870）；江西省自然科学基金项目（20224BAB206099）；江西省教育厅科研项目（GJJ2200910）；江西省 中医药管理局科技计划项目（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）。