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叶春荣, 姚文林, 胡露楠, 陈淑游, 张晓源, 万丹, 俞静.基于Nrf2/HO-1信号通路调控巨噬细胞极性探讨复方胃炎合剂干预胃癌前病变的机制[J].湖南中医药大学学报英文版,2026,46(1):23-30.[Click to copy
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| 基于Nrf2/HO-1信号通路调控巨噬细胞极性探讨复方胃炎合剂干预胃癌前病变的机制 |
| 叶春荣,姚文林,胡露楠,陈淑游,张晓源,万丹,俞静 |
| (福建中医药大学附属第二人民医院, 福建 福州 350003;福建中医药大学, 福建 福州 350122) |
| 摘要: |
| 目的 探讨复方胃炎合剂通过调控巨噬细胞极性治疗胃癌前病变的作用机制。方法 将Wistar大鼠分为空白组（6只）及造模组（33只）。造模组采用复合因素诱导法构建胃癌前病变大鼠模型，造模成功后分为模型组，复方胃炎合剂低、中、高剂量组[2.5、5、10 mL/（kg·d）复方胃炎合剂溶液灌胃]，维酶素组[0.2 g/（kg·d）维酶素混悬液灌胃]，每组6只。使用相应药物干预4周后，观察大鼠整体情况（尾巴、体形），记录体质量增长情况，HE染色观察胃黏膜组织结构变化，qPCR检测白细胞介素（IL）-12、IL-23、IL-4、精氨酸-1（Arg-1）mRNA相对表达量，Western blot检测核因子E2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）、白细胞分化抗原（CD）16、CD206蛋白相对表达量。结果 与空白组比较，模型组大鼠尾巴细短、色泽较瘀暗，体形明显减小，体质量增长缓慢，胃黏膜组织细胞异型增生明显，Arg-1、IL-4 mRNA及CD16蛋白相对表达量升高（P＜0.05），IL-23、IL-12 mRNA及CD206、HO-1、Nrf2蛋白相对表达量降低（P＜0.05）。与模型组比较，复方胃炎合剂低、中、高剂量组大鼠整体情况改善，胃黏膜组织结构重塑，腺体萎缩显著改善，异型增生及肠上皮化生明显减少；复方胃炎合剂低、中、高剂量组和维酶素组Arg-1 mRNA及CD16蛋白相对表达量降低（P＜0.05），HO-1蛋白相对表达量升高（P＜0.05）；复方胃炎合剂中、高剂量组及维酶素组IL-12 mRNA及Nrf2、CD206蛋白相对表达量升高（P＜0.05）；复方胃炎合剂高剂量组和维酶素组IL-4 mRNA相对表达量降低（P＜0.05）；复方胃炎合剂高剂量组IL-23 mRNA相对表达量升高（P＜0.05）。与维酶素组比较，复方胃炎合剂高剂量组IL-12 mRNA相对表达量升高；复方胃炎合剂低、中、高剂量组HO-1蛋白相对表达量降低（P＜0.05）；复方胃炎合剂低、中剂量组Nrf2和复方胃炎合剂低、中、高剂量组CD206蛋白相对表达量降低（P＜0.05）；复方胃炎合剂低、中剂量组CD16蛋白相对表达量升高（P＜0.05）。结论 复方胃炎合剂可通过调控Nrf2/HO-1信号通路，抑制氧化应激，进而影响巨噬细胞极性，实现对胃黏膜肠上皮化生与异型增生的控制或逆转，从而发挥抗胃癌前病变的作用。 |
| 关键词: 胃癌前病变 复方胃炎合剂 氧化应激 巨噬细胞极性 胃癌 Nrf2/HO-1信号通路 |
| DOI：10.3969/j.issn.1674-070X.2026.01.004 |
| Received:August 05, 2025 |
| 基金项目:福建省自然科学基金项目（2023J01811）。 |
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| Mechanistic investigation of compound gastritis mixture in precancerous lesions of gastric cancer via regulation of macrophage polarization mediated by the Nrf2/HO-1 signaling pathway |
| YE Chunrong, YAO Wenlin, HU Lu'nan, CHEN Shuyou, ZHANG Xiaoyuan, WAN Dan, YU Jing |
| (The Second People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, China;Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China) |
| Abstract: |
| Objective To investigate the mechanism of action by which compound gastritis mixture (CGM) regulates macrophage polarization in the treatment of precancerous lesions of gastric cancer (PLGC). Methods Wistar rats were divided into blank group (n=6) and modeling group (n=33). The modeling group was used to establish a rat model of precancerous gastric lesions by compound factor induction. After successful modeling, the rats were further divided into a model group, CGM low-, medium-, and high-dose groups [2.5, 5, and 10 mL/(kg·d) CGM solution by gavage], and a vitacoenzyme group [0.2 g/(kg·d) vitacoenzyme suspension by gavage], with six rats in each group. After four weeks of intervention with the respective drugs, the general condition of the rats (tail, body shape) was observed, and body weight gain was recorded. Changes in gastric mucosal tissue structure were examined by hematoxylin-eosin (HE) staining. Relative messenger ribonucleic acid (mRNA) expression levels of interleukin (IL)-12, IL-23, IL-4, and arginase-1 (Arg-1) were measured by quantitative polymerase chain reaction (qPCR). Relative protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), cluster of differentiation (CD)16, and CD206 were detected by Western blot. Results Compared with the blank group, rats in the model group exhibited short, thin tails with a dark purplish coloration, a markedly smaller body size, slow body-weight gain, and obvious dysplastic changes in gastric mucosal tissues. The relative mRNA expression levels of Arg-1 and IL-4 and the relative protein expression level of CD16 increased (P＜0.05), whereas the relative mRNA expression levels of IL-23 and IL-12 and the relative protein expression levels of CD206, HO-1, and Nrf2 decreased (P＜0.05). Compared with the model group, the overall condition of rats improved in the CGM low-, medium-, and high-dose groups, the gastric mucosal structure was remodeled, glandular atrophy was significantly alleviated, and dysplasia and intestinal metaplasia markedly reduced; the relative mRNA expression level of Arg-1 and the relative protein expression level of CD16 decreased in the CGM low-, medium-, and high-dose groups and the vitacoenzyme group (P＜0.05), while the relative protein expression level of HO-1 increased (P＜0.05); the relative mRNA expression level of IL-12 and the relative protein expression levels of Nrf2 and CD206 increased in the CGM medium- and high-dose groups and the vitacoenzyme group (P＜0.05); the relative mRNA expression level of IL-4 decreased in the CGM high-dose group and the vitacoenzyme group (P＜0.05); the relative mRNA expression level of IL-23 increased in the CGM high-dose group (P＜0.05). Compared with the vitacoenzyme group, the relative mRNA expression level of IL-12 increased in the CGM high-dose group; the relative protein expression level of HO-1 decreased in the CGM low-, medium-, and high-dose groups (P＜0.05); the relative protein expression level of Nrf2 decreased in the CGM low- and medium-dose groups, and the relative protein expression level of CD206 decreased in the CGM low-, medium-, and high-dose groups (P＜0.05); the relative protein expression level of CD16 increased in the CGM low- and medium-dose groups (P＜0.05). Conclusion Compound gastritis mixture may regulate the Nrf2/HO-1 signaling pathway to inhibit oxidative stress, thereby affecting macrophage polarization and achieving control or reversal of intestinal metaplasia and dysplasia of the gastric mucosa, exerting a protective effect against PLGC. |
| Key words: precancerous lesions of gastric cancer compound gastritis mixture oxidative stress macrophage polarization gastric cancer Nrf2/HO-1 signaling pathway |
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