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经皮耳迷走神经刺激通过减少 BALB/c 小鼠中性粒细胞浸润来减轻痛风性炎症。

Transcutaneous auricular vagus nerve stimulation mitigates gouty inflammation by reducing neutrophil infiltration in BALB/c mice.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Guro Hospital, 80 Guro-dong, Guro-gu, Seoul, 08308, Korea.

Institute for Health Care Convergence Center, Korea University Guro Hospital, Seoul, 08308, Korea.

出版信息

Sci Rep. 2024 Oct 27;14(1):25630. doi: 10.1038/s41598-024-77272-2.

DOI:10.1038/s41598-024-77272-2
PMID:39463429
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11514149/
Abstract

Gouty inflammation, caused by uric acid crystal deposition, primarily affects tissues around the toe joints and triggers potent inflammatory responses. Current treatments focus on alleviating inflammation and pain using pharmaceutical agents, which can lead to side effects and complications. This has generated interest in non-pharmacological interventions, such as non-invasive vagus nerve stimulation (VNS). In this study, we explored the anti-inflammatory mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of acute gout. Gouty inflammation was induced by injecting monosodium urate (MSU) crystals into the ankle joints of BALB/c mice. The effects of taVNS on the expression of inflammatory cytokines and chemokines in the ankle joint tissue were assessed using real-time quantitative PCR (qPCR), western blotting, histological assessments (H&E staining), and immunohistochemistry (IHC). The role of α7 nicotinic acetylcholine receptors (α7nAChR) was also evaluated by signal blocking. Our findings revealed that MSU significantly elevated gout-associated inflammatory cascades and mediators in the ankle joint. Notably, taVNS at 200 µA and 25 Hz effectively reduced these inflammatory responses, decreasing neutrophil infiltration and chemoattraction within the tissue. taVNS showed significant anti-inflammatory properties by suppressing neutrophil activity, offering a novel therapeutic approach for gout beyond conventional pharmacological methods. Additionally, taVNS holds potential for managing various chronic joint diseases. These results highlight taVNS as a promising non-pharmacological therapy for chronic inflammation.

摘要

痛风性炎症由尿酸晶体沉积引起,主要影响脚趾关节周围的组织,并引发强烈的炎症反应。目前的治疗方法侧重于使用药物来缓解炎症和疼痛,这可能会导致副作用和并发症。这引发了人们对非药物干预措施的兴趣,例如非侵入性迷走神经刺激(VNS)。在这项研究中,我们探讨了经皮耳迷走神经刺激(taVNS)在急性痛风小鼠模型中的抗炎机制。通过将尿酸单钠(MSU)晶体注射到 BALB/c 小鼠的踝关节中来诱导痛风性炎症。使用实时定量 PCR(qPCR)、Western blot、组织学评估(H&E 染色)和免疫组织化学(IHC)评估 taVNS 对踝关节组织中炎症细胞因子和趋化因子表达的影响。还通过信号阻断评估了α7 烟碱型乙酰胆碱受体(α7nAChR)的作用。我们的研究结果表明,MSU 显著升高了踝关节中的痛风相关炎症级联和介质。值得注意的是,200 µA 和 25 Hz 的 taVNS 可有效降低这些炎症反应,减少组织内的中性粒细胞浸润和趋化作用。taVNS 通过抑制中性粒细胞活性显示出显著的抗炎特性,为痛风提供了一种超越传统药物方法的新的治疗方法。此外,taVNS 还可能用于治疗各种慢性关节疾病。这些结果强调了 taVNS 作为慢性炎症的一种有前途的非药物治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/11514149/40899d0fd6b4/41598_2024_77272_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/11514149/98c4e1a6c76d/41598_2024_77272_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/11514149/8344a2fa7d64/41598_2024_77272_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/11514149/40899d0fd6b4/41598_2024_77272_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/11514149/98c4e1a6c76d/41598_2024_77272_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/11514149/5f386a97647d/41598_2024_77272_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/11514149/2a6cf18e94f0/41598_2024_77272_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/11514149/70a6178cd9a3/41598_2024_77272_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/11514149/8344a2fa7d64/41598_2024_77272_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/11514149/40899d0fd6b4/41598_2024_77272_Fig6_HTML.jpg

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本文引用的文献

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Cells. 2023 Nov 13;12(22):2621. doi: 10.3390/cells12222621.
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Different Transcutaneous Auricular Vagus Nerve Stimulation Parameters Modulate the Anti-Inflammatory Effects on Lipopolysaccharide-Induced Acute Inflammation in Mice.不同的经皮耳迷走神经刺激参数调节对脂多糖诱导的小鼠急性炎症的抗炎作用。
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