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氧化应激失衡与鼻息肉慢性鼻窦炎的发病机制有关。

The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps.

机构信息

Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.

Upper Respiratory Tract Laboratory of Department of Otolaryngology-Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Front Immunol. 2024 May 2;15:1380846. doi: 10.3389/fimmu.2024.1380846. eCollection 2024.

Abstract

BACKGROUND

Although oxidative stress is involved in the pathophysiological process of chronic rhinosinusitis with nasal polyps (CRSwNP), the specific underlying mechanism is still unclear. Whether antioxidant therapy can treat CRSwNP needs further investigation.

METHODS

Immunohistochemistry, immunofluorescence, western blotting and quantitative polymerase chain reaction (qPCR) analyses were performed to detect the distribution and expression of oxidants and antioxidants in nasal polyp tissues. qPCR revealed correlations between oxidase, antioxidant enzymes and inflammatory cytokine levels in CRSwNP patients. Human nasal epithelial cells (HNEpCs) and primary macrophages were cultured to track the cellular origin of oxidative stress in nasal polyps(NPs) and to determine whether crocin can reduce cellular inflammation by increasing the cellular antioxidant capacity.

RESULTS

The expression of NOS2, NOX1, HO-1 and SOD2 was increased in nasal epithelial cells and macrophages derived from nasal polyp tissue. Oxidase levels were positively correlated with those of inflammatory cytokines (IL-5 and IL-6). Conversely, the levels of antioxidant enzymes were negatively correlated with those of IL-13 and IFN-γ. Crocin inhibited M1 and M2 macrophage polarization as well as the expression of NOS2 and NOX1 and improved the antioxidant capacity of M2 macrophages. Moreover, crocin enhanced the ability of antioxidants to reduce inflammation via the KEAP1/NRF2/HO-1 pathway in HNEpCs treated with SEB or LPS. Additionally, we observed the antioxidant and anti-inflammatory effects of crocin in nasal explants.

CONCLUSION

Oxidative stress plays an important role in the development of CRSwNP by promoting various types of inflammation. The oxidative stress of nasal polyps comes from epithelial cells and macrophages. Antioxidant therapy may be a promising strategy for treating CRSwNP.

摘要

背景

尽管氧化应激参与了慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)的病理生理过程,但具体的潜在机制仍不清楚。抗氧化治疗是否能治疗 CRSwNP 还需要进一步研究。

方法

通过免疫组化、免疫荧光、western blot 和定量聚合酶链反应(qPCR)分析,检测鼻息肉组织中氧化剂和抗氧化剂的分布和表达。qPCR 揭示了 CRSwNP 患者氧化酶、抗氧化酶和炎症细胞因子水平之间的相关性。培养人鼻上皮细胞(HNEpCs)和原代巨噬细胞,以追踪鼻息肉(NPs)中氧化应激的细胞起源,并确定藏红花酸是否可以通过增加细胞抗氧化能力来减轻细胞炎症。

结果

NOS2、NOX1、HO-1 和 SOD2 在鼻上皮细胞和鼻息肉组织来源的巨噬细胞中的表达增加。氧化酶水平与炎症细胞因子(IL-5 和 IL-6)呈正相关。相反,抗氧化酶的水平与 IL-13 和 IFN-γ 呈负相关。藏红花酸抑制 M1 和 M2 巨噬细胞极化以及 NOS2 和 NOX1 的表达,并改善 M2 巨噬细胞的抗氧化能力。此外,藏红花酸通过 SEB 或 LPS 处理的 HNEpCs 中的 KEAP1/NRF2/HO-1 通路增强了抗氧化剂降低炎症的能力。此外,我们观察到藏红花酸在鼻外植体中的抗氧化和抗炎作用。

结论

氧化应激通过促进各种类型的炎症在 CRSwNP 的发展中起重要作用。鼻息肉的氧化应激来自于上皮细胞和巨噬细胞。抗氧化治疗可能是治疗 CRSwNP 的一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd9e/11096511/2f7ff74d1493/fimmu-15-1380846-g001.jpg

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