Zheng Furong, Zhang Xin, Wang Sisi, Jia Gongwei, Cheng Li
Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Health Management Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Biomedicines. 2025 May 24;13(6):1294. doi: 10.3390/biomedicines13061294.
Acute respiratory distress syndrome (ARDS) is a high-mortality disease strongly associated with an imbalance in the inflammatory response. The ratio of helper T 17 (Th17) cells to regulatory T (Treg) cells is significantly correlated with prognosis and outcomes in ARDS. Vagus nerve stimulation (VNS) alleviates lung injury in ARDS model rats. The objective of this study was to further investigate whether VNS attenuates lipopolysaccharide-induced ARDS by regulating Th17/Treg homeostasis and to explore the underlying mechanisms. : We assessed the degree of lung injury using hematoxylin and eosin staining, the lung wet-to-dry ratio, and total protein and pro-inflammatory cytokine levels in bronchoalveolar lavage fluid. The expression levels of Th17 and Treg cells were determined using flow cytometry, Western blotting, quantitative real-time PCR, and enzyme-linked immunosorbent assays. : We found that VNS reduced lung injury in ARDS model rats. Additionally, VNS regulated Th17/Treg homeostasis and reduced the levels of inflammatory factors in both the lungs and spleens. Notably, the effects of VNS were consistent when the afferent or efferent vagus nerve, or both, were stimulated. Further investigation revealed that VNS upregulated splenic α7 nicotinic acetylcholine receptors (α7nAChRs). The administration of an α7nAChR agonist enhanced VNS-mediated regulation of Th17/Treg homeostasis and attenuated lung injury, while these effects were blocked by α7nAChR antagonists. : Our study demonstrated that VNS regulates the Th17/Treg balance through α7nAChR activation in the spleen, thereby mitigating lung injury in ARDS. These findings provide new theoretical support for the use of VNS in attenuating ARDS.
急性呼吸窘迫综合征（ARDS）是一种死亡率很高的疾病，与炎症反应失衡密切相关。辅助性T细胞17（Th17）与调节性T（Treg）细胞的比例与ARDS的预后和结局显著相关。迷走神经刺激（VNS）可减轻ARDS模型大鼠的肺损伤。本研究的目的是进一步探讨VNS是否通过调节Th17/Treg平衡来减轻脂多糖诱导的ARDS，并探索其潜在机制。我们使用苏木精和伊红染色、肺湿干比以及支气管肺泡灌洗液中的总蛋白和促炎细胞因子水平来评估肺损伤程度。使用流式细胞术、蛋白质免疫印迹法、定量实时聚合酶链反应和酶联免疫吸附测定法来测定Th17和Treg细胞的表达水平。我们发现VNS可减轻ARDS模型大鼠的肺损伤。此外，VNS调节Th17/Treg平衡，并降低肺和脾脏中的炎症因子水平。值得注意的是，刺激传入或传出迷走神经或两者同时刺激时，VNS的效果是一致的。进一步研究发现，VNS上调脾脏α7烟碱型乙酰胆碱受体（α7nAChRs）。给予α7nAChR激动剂可增强VNS介导的对Th17/Treg平衡的调节并减轻肺损伤，而这些作用被α7nAChR拮抗剂阻断。我们的研究表明，VNS通过激活脾脏中的α7nAChR来调节Th17/Treg平衡，从而减轻ARDS中的肺损伤。这些发现为使用VNS减轻ARDS提供了新的理论支持。
