杆菌核通过破坏NOX4/NRF2平衡来驱动内皮细胞衰老
Peiyao Wu1,2, Jieyu Zhou1,2, Jun Wang1,2
1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
mBio
|January 8, 2026
概括
菌核酸菌感染通过氧化应激导致内皮细胞衰老,加速动脉样硬化. 向NOX4或GSK3β可能会恢复血管功能并预防与衰老有关的心血管疾病.
科学领域:
- 心血管研究研究心血管研究
- 微生物学 微生物学
- 细胞衰老 细胞衰老
背景情况:
- 内皮细胞衰老是动脉样硬化发展的关键因素.
- 牙周病原体Fusobacterium nucleatum (Fn) 有助于动脉样硬化的作用.
- 对于Fn在内皮衰老中的作用尚不清楚.
研究的目的:
- 调查Fn是否以及如何诱导内皮老化.
- 为了探索Fn对动脉样硬化的贡献.
- 为了阐明底层的分子机制.
主要方法:
- 在体内研究涉及动物模型的慢性Fn感染.
- 在体外实验中对暴露于Fn.的内皮细胞进行实验.
- 对氧化应激标志物,氧化还原平衡和细胞衰老的分析.
- 研究NOX4/NRF2信号通路及其由AKT/GSK3β.调节的研究.
主要成果:
- 慢性Fn感染加速了动脉样硬化,增加了氧化应激,血管衰老,以及体内内皮质功能受损.
- 在实验室中,Fn诱导了剂量和时间依赖的ROS产生,破坏了氧化还原平衡,并促进了衰老和功能障碍.
- 长时间的Fn感染抑制了NRF2活性,持续NOX4上调,并通过AKT脱和GSK3β激活加剧了氧化应激.
- 抑制NOX4或GSK3β恢复了氧化还原平衡,减少衰老,并改善了内皮功能.
结论:
- 通过NOX4/NRF2轴不平衡,Fn驱动了内皮衰老和动脉样硬化的进展.
- 向NOX4或GSK3β为与慢性口腔感染相关的血管衰老和动脉样硬化提供了潜在的治疗策略.
- 慢性口腔感染可能导致血管衰老和心血管疾病,强调口腔健康的系统重要性.
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