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武泓岚, 王巧玥, 孟虹宇, 孙菲飞, 江婕妤, 吴利法, 夏旭婷, 刘富林.高氧戊己汤调控MyD88/NLRP3/Caspase-1信号通路相关蛋白及肠道菌群稳态抗Hp感染的机制[J].湖南中医药大学学报英文版,2026,46(7):1355-1364.[Click to copy
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| 高氧戊己汤调控MyD88/NLRP3/Caspase-1信号通路相关蛋白及肠道菌群稳态抗Hp感染的机制 |
| 武泓岚,王巧玥,孟虹宇,孙菲飞,江婕妤,吴利法,夏旭婷,刘富林 |
| (湖南中医药大学, 湖南 长沙 410208;宁乡市中医医院, 湖南 宁乡 410600;益阳市第一中医医院, 湖南 益阳 413000;浏阳市中医医院, 湖南 浏阳 410300) |
| 摘要: |
| 目的 基于髓系分化初级反应蛋白质88（MyD88）/NOD样受体热蛋白结构域相关蛋白3（NLRP3）/胱天蛋白酶1（Caspase-1）信号通路与肠道菌群稳态，探讨高氧戊己汤抗幽门螺杆菌（Hp）感染保护小鼠胃黏膜的作用机制。方法 将38只小鼠随机分为空白组11只、造模组27只。造模完成后，从两组中各随机选取3只小鼠，采用快速尿素酶试验判断模型构建是否成功。造模成功后，将造模组小鼠随机分为模型组、高氧戊己汤组、西药组（四联疗法），每组8只。高氧戊己汤组和西药组分别予灌胃对应药液0.2 mL，空白组、模型组予灌胃蒸馏水0.2 mL，连续干预14 d。采用HE染色观察小鼠胃黏膜病理变化；Warthin-Starry银染色检测小鼠胃黏膜Hp定植情况；ELISA检测小鼠胃黏膜核因子κB（NF-κB）、白细胞介素-1β（IL-1β）含量；Western blot及RT-qPCR检测胃黏膜MyD88、NLRP3、Caspase-1蛋白及mRNA表达水平；比色法检测丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性；16S rDNA测序分析肠道菌群多样性与结构变化。结果 与空白组比较，模型组小鼠胃黏膜损伤明显，Hp大量定植，NF-κB、IL-1β、MDA含量、SOD活性均升高（P<0.01），MyD88、NLRP3、Caspase-1蛋白及mRNA表达水平均升高（P<0.01）。与模型组比较，西药组和高氧戊己汤组小鼠胃黏膜病理损伤减轻，Hp定植减少，NF-κB、IL-1β、MDA含量、SOD活性均降低（P<0.01），MyD88、NLRP3、Caspase-1蛋白及mRNA表达水平均降低（P<0.05，P<0.01）。16S rDNA测序显示，与空白组比较，模型组肠道菌群Chao1、Observed_species、Shannon及Simpson指数均下降；与模型组比较，高氧戊己汤组菌群（Chao1、Observed_species指数）丰富度呈升高趋势，且能恢复β多样性，同时调节门/属水平的物种组成（降低厚壁菌门/拟杆菌门比值），而西药组则进一步加剧菌群失调。结论 高氧戊己汤能抗Hp感染并保护胃黏膜，其机制可能与通过调控MyD88/NLRP3/Caspase-1信号通路抑制炎症及氧化应激双重反应，同时重塑肠道菌群结构与稳态密切相关。 |
| 关键词: 高氧戊己汤|幽门螺杆菌|MyD88/NLRP3/Caspase-1信号通路|炎症|氧化应激|肠道菌群 |
| DOI：10.3969/j.issn.1674-070X.2026.07.006 |
| Received:April 13, 2026 |
| 基金项目:湖南省自然科学基金项目（2024JJ7359）；湖南省自然科学联合基金重点项目（2026JJ30090）；湖南省教育厅重点项目（25A0289，23A0292）；中药粉体与创新药物省部共建国家重点实验室培育基地开放基金重点项目（24PTKF1001）。 |
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| Mechanism of hyperoxic Wuji Decoction against Helicobacter pylori infection by regulating MyD88/NLRP3/Caspase-1 signaling pathway related proteins and gut microbiota |
| WU Honglan, WANG Qiaoyue, MENG Hongyu, SUN Feifei, JIANG Jieyu, WU Lifa, XIA Xuting, LIU Fulin |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Ningxiang Hospital of Traditional Chinese Medicine, Ningxiang, Hunan 410600, China;Yiyang First Hospital of Traditional Chinese Medicine, Yiyang, Hunan 413000, China;Liuyang Hospital of Traditional Chinese Medicine, Liuyang, Hunan 410300, China) |
| Abstract: |
| Objective To investigate the mechanism of action of hyperoxic Wuji Decoction (WJD) in protecting against Helicobacter pylori (Hp) infection-induced gastric mucosal injury in mice, based on the myeloid differentiation primary response protein 88/NOD-like receptor family pyrin domain-containing protein 3/cysteinyl aspartate-specific proteinase 1 (MyD88/NLRP3/Caspase-1) signaling pathway and gut microbiota homeostasis. Methods 38 mice were randomly divided into blank group (n=11) and modeling group (n=27). After modeling, 3 mice were randomly selected from each group to verify the success of modeling by rapid urease test. Then the successfully modeled mice were randomly divided into model group, hyperoxic WJD group, and Western medicine group (quadruple therapy group), with 8 mice in each group. Hyperoxic WJD group and the Western medicine group were administered 0.2 mL of their respective drug solutions by gavage daily, while the blank group and the model group received 0.2 mL of distilled water by gavage daily, for 14 consecutive days. After intervention, pathological changes of gastric mucosa were observed by HE staining; Hp colonization in gastric mucosa was checked by Warthin-Starry silver staining; the levels of NF-κB and IL-1β in gastric mucosa were tested by ELISA; protein and mRNA expression levels of MyD88, NLRP3, and Caspase-1 in gastric mucosa were measured by Western blot and RT-qPCR; MDA content and SOD activity were determined by colorimetric assay; and the diversity and structure of gut microbiota were analyzed by 16S rDNA sequencing. Results Compared with the blank group, the model group showed obvious gastric mucosal injury, massive Hp colonization, significantly increased NF-κB, IL-1β, MDA content and SOD activity (P<0.01), significantly upregulated protein and mRNA expressions of MyD88, NLRP3 and Caspase-1 (P<0.01). Compared with the model group, both the hyperoxic WJD group and the quadruple therapy group alleviated gastric mucosal pathological injury, reduced Hp colonization, decreased levels of NF-κB, IL-1β, MDA content and SOD activity(P<0.01), and decreased protein and mRNA expressions of MyD88, NLRP3 and Caspase-1 (P<0.05, P<0.01). 16S rDNA sequencing revealed that compared with the blank group, the model group exhibited decreased Chao1, Observed species, Shannon, and Simpson indices (P<0.05, P<0.01). Compared with the model group, hyperoxic WJD group indicated an increasing trend in species (Chao1 and Observed species) richness (P>0.05), restored β-diversity, and modulated phylum/genus-level species composition (reducing the Firmicutes/Bacteroidota ratio), whereas the Western medicine group further exacerbated gut microbiota dysbiosis. Conclusion Hyperoxic WJD can protect the gastric mucosa against Hp infection. Its mechanism may be closely related to regulating the MyD88/NLRP3/Caspase-1 signaling pathway to inhibit the dual responses of inflammation and oxidative stress, and remodeling the structure and homeostasis of gut microbiota. |
| Key words: hyperoxic Wuji Decoction|Helicobacter pylori|MyD88/NLRP3/Caspase-1 signaling pathway|inflammation|oxidative stress|gut microbiota |
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