湖南中医药大学学报2026，Vol.46Issue(1)：23-30,8.DOI:10.3969/j.issn.1674-070X.2026.01.004
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
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
摘要
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.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Key words
precancerous lesions of gastric cancer/compound gastritis mixture/oxidative stress/macrophage polarization/gastric cancer/Nrf2/HO-1 signaling pathway分类
医药卫生引用本文复制引用
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,2026,46(1):23-30,8.基金项目
福建省自然科学基金项目(2023J01811). （2023J01811）
