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麝香酮在慢性阻塞性肺疾病发生发展中的保护作用。

The protective role of muscone in the development of COPD.

作者信息

Feng Tiantian, Guo Xiaolong, Chen Wei, Zhang Yanying, Dai Runjing, Zhang Yinfang, Liu Yongqi, Liu Yiya, Song Peng, Fan Jingchun

机构信息

School of Public Health, Centre for Evidence-Based Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.

Quality Assurance Department, Lanzhou Institute of Biological Products Co., Ltd, Lanzhou, Gansu, China.

出版信息

Front Immunol. 2025 Feb 17;16:1508879. doi: 10.3389/fimmu.2025.1508879. eCollection 2025.

Abstract

BACKGROUND

Muscone, a key component of musk, exhibits anti-inflammatory properties. However, its therapeutic potential in inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD), remains largely unexplored. This study aimed to investigate whether Muscone could exert a protective effect in a mouse model of COPD .

METHODS

A COPD animal model was established by exposing mice to cigarette smoke (CS) and administering lipopolysaccharide (LPS) intranasally. After 4 weeks, mice were treated daily with dexamethasone (DEX) or different doses of Muscone for 3 weeks. Mouse body weight, lung function, and histopathology were determined. Serum levels of cytokines (IL-38, IL-1β, IL-17, TGF-β, IFN-γ) were measured using ELISA and qRT-PCR. Lung expression of CXCR3, IFN-γ, IL-17A, and RORγt was assessed by immunofluorescence.

RESULTS

The body weight of COPD mice was significantly lower than that of Muscone-treated COPD mice, consistent with decreased lung function, accompanied by reduced circulating and lung IL-38 levels. After Muscone administration, lung function was significantly improved, accompanied by upregulation of circulating and lung anti-inflammatory cytokines, including IL-38, in a dose-dependent manner, while the expression of pro-inflammatory cytokines was significantly reduced. Additionally, Muscone significantly inhibited the protein expression of CXCR3, IFN-γ, IL-17A, and RORγt in lung tissues of COPD mice.

CONCLUSION

This study demonstrates that Muscone improves lung function in mice with COPD, potentially through a mechanism that may involve the modulation of cytokine expression, including the potential upregulation of anti-inflammatory cytokines such as IL-38. The precise underlying mechanisms of Muscone's therapeutic effects in COPD remain to be fully elucidated. Further research is needed to investigate the correlation between COPD lung pathophysiology and the specific effects of Muscone treatment, including a more detailed analysis of the balance between pro- and anti-inflammatory mediators in COPD animal models, particularly utilizing IL-38 GKO mice to further investigate the role of IL-38 in mediating the therapeutic effects of Muscone.

摘要

背景

麝香酮是麝香的关键成分,具有抗炎特性。然而,其在慢性阻塞性肺疾病(COPD)等炎症性肺部疾病中的治疗潜力在很大程度上仍未得到探索。本研究旨在探讨麝香酮是否能在COPD小鼠模型中发挥保护作用。

方法

通过让小鼠暴露于香烟烟雾(CS)并经鼻给予脂多糖(LPS)建立COPD动物模型。4周后,小鼠每天接受地塞米松(DEX)或不同剂量的麝香酮治疗3周。测定小鼠体重、肺功能和组织病理学。使用酶联免疫吸附测定法(ELISA)和定量逆转录聚合酶链反应(qRT-PCR)测量细胞因子(IL-38、IL-1β、IL-17、转化生长因子-β、干扰素-γ)的血清水平。通过免疫荧光评估肺组织中CXC趋化因子受体3(CXCR3)、干扰素-γ、IL-17A和维甲酸相关孤儿受体γt(RORγt)的表达。

结果

COPD小鼠的体重显著低于接受麝香酮治疗的COPD小鼠,这与肺功能下降一致,同时循环和肺组织中的IL-38水平降低。给予麝香酮后,肺功能显著改善,同时循环和肺组织中的抗炎细胞因子(包括IL-38)呈剂量依赖性上调,而促炎细胞因子的表达显著降低。此外,麝香酮显著抑制COPD小鼠肺组织中CXCR3、干扰素-γ、IL-17A和RORγt的蛋白表达。

结论

本研究表明,麝香酮可改善COPD小鼠的肺功能,其潜在机制可能涉及细胞因子表达的调节,包括抗炎细胞因子如IL-38的潜在上调。麝香酮在COPD中的治疗作用的确切潜在机制仍有待充分阐明。需要进一步研究来探讨COPD肺病理生理学与麝香酮治疗的具体效果之间的相关性,包括对COPD动物模型中促炎和抗炎介质平衡进行更详细的分析,特别是利用IL-38基因敲除小鼠进一步研究IL-38在介导麝香酮治疗效果中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d3/11872711/f3a5c445b9c1/fimmu-16-1508879-g001.jpg

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