幽门螺杆菌感染通过NRF2/KEAP1通路激活与声带白斑的发生和进展相关
Helicobacter pylori Infection Is Associated With the Occurrence and Progression of Vocal Fold Leukoplakia via NRF2/KEAP1 Pathway Activation.
文献信息
| PMID | 42944642 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Jiajia Shi |
| 作者单位 | ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China. |
| 期刊 | International journal of cancer |
| SCI 分区 | Q2 |
| IF | 5.8 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 咽喉科 |
中文摘要
背景： 幽门螺杆菌（H. pylori）感染被认为与声带白斑（VFL）这一喉癌前病变有关。然而，其潜在机制仍不清楚。本研究探讨了H. pylori与VFL之间的关系，重点关注NRF2/KEAP1氧化应激通路。方法：对64例VFL患者和30例声带息肉患者（对照）的样本进行了临床病理学分析。结果：结果显示，VFL组H. pylori的检出率（48.4%）显著高于对照组（16.7%，p = 0.003）。在H. pylori阳性的VFL病例中，VacA阳性菌株占主导，占71.0%。多因素logistic回归确定H. pylori是VFL的独立危险因素（OR = 6.198，95% CI：1.580-24.321）。VFL组织表现出NRF2、KEAP1和HO-1表达上调（p < 0.001），显示出毒力依赖性（HO-1诱导）和毒力非依赖性（NRF2上调）两种通路激活模式。体外实验显示，H. pylori暴露诱导NRF2核转位并触发氧化应激反应。值得注意的是，VFL来源的细胞对H. pylori刺激反应更迅速，通路激活在感染后24小时达到峰值，而正常细胞反应延迟，在48小时达到峰值（p < 0.05）。此外，H. pylori暴露后，VFL来源的细胞表现出更明显的应激诱导形态学改变。结论：这些发现表明，H. pylori可能通过NRF2/KEAP1通路激活促进VFL进展，突显了H. pylori筛查在VFL管理中的潜在临床价值。
英文摘要
Helicobacter pylori (H. pylori) infection has been implicated in vocal fold leukoplakia (VFL), a precancerous laryngeal lesion. However, the underlying mechanisms remain unclear. This study investigated the relationship between H. pylori and VFL, focusing on the NRF2/KEAP1 oxidative stress pathway. Clinicopathological analysis was performed on samples from 64 patients with VFL and 30 patients with vocal cord polyps (controls). The results showed a significantly higher prevalence of H. pylori in the VFL group (48.4%) than in the controls (16.7%, p = 0.003). Among H. pylori-positive VFL cases, VacA-positive strains predominated, accounting for 71.0%. Multivariate logistic regression identified H. pylori as an independent risk factor for VFL (OR = 6.198, 95% CI: 1.580-24.321). VFL tissues exhibited upregulated expression of NRF2, KEAP1, and HO-1 (p < 0.001), demonstrating both virulence-dependent (HO-1 induction) and virulence-independent (NRF2 upregulation) pathway activation patterns. In vitro experiments revealed that H. pylori exposure induced NRF2 nuclear translocation and triggered an oxidative stress response. Notably, VFL-derived cells responded more rapidly to H. pylori stimulation, with pathway activation peaking at 24 h post-infection, whereas normal cells showed a delayed response, peaking at 48 h (p < 0.05). Furthermore, VFL-derived cells displayed more pronounced stress-induced morphological alterations following H. pylori exposure. These findings suggest that H. pylori may promote VFL progression via NRF2/KEAP1 pathway activation, highlighting the potential clinical value of H. pylori screening in VFL management.