Table 4_The protective role of muscone in the development of COPD.xlsx

BackgroundMuscone, 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 in vivo.
MethodsA 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.
ResultsThe 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.
ConclusionThis 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.

背景：麝香酮（Muscone）作为麝香的关键活性组分，具有明确的抗炎特性。然而其在慢性阻塞性肺疾病（COPD）这类炎症性肺部疾病中的治疗潜力，迄今仍未得到充分探索。本研究旨在探究麝香酮在体内COPD小鼠模型中是否能够发挥保护作用。
方法：本研究通过香烟烟雾（CS）暴露联合鼻内给予脂多糖（LPS）构建COPD动物模型。造模4周后，每日给予地塞米松（DEX）或不同剂量的麝香酮干预，持续3周。随后检测小鼠体重、肺功能及组织病理学变化；采用酶联免疫吸附试验（ELISA）与实时定量聚合酶链反应（qRT-PCR）测定血清细胞因子白细胞介素-38（IL-38）、白细胞介素-1β（IL-1β）、白细胞介素-17（IL-17）、转化生长因子-β（TGF-β）、干扰素-γ（IFN-γ）的水平；通过免疫荧光法检测肺组织中CXC趋化因子受体3（CXCR3）、干扰素-γ（IFN-γ）、白细胞介素-17A（IL-17A）及视黄酸相关孤儿受体γt（RORγt）的表达情况。
结果：COPD模型小鼠的体重显著低于麝香酮干预组小鼠，同时伴随肺功能下降以及循环与肺组织中IL-38水平降低。给予麝香酮干预后，小鼠肺功能得到显著改善，且循环与肺组织中的抗炎细胞因子（包括IL-38）表达呈剂量依赖性上调，促炎细胞因子表达则显著降低。此外，麝香酮可显著抑制COPD模型小鼠肺组织中CXCR3、IFN-γ、IL-17A及RORγt的蛋白表达。
结论：本研究证实，麝香酮可改善COPD模型小鼠的肺功能，其潜在机制可能涉及调控细胞因子表达，包括上调IL-38等抗炎细胞因子。然而麝香酮治疗COPD的确切分子机制仍有待完全阐明。未来需进一步探究COPD肺部病理生理与麝香酮治疗的特定效应之间的关联，例如更细致地分析COPD动物模型中促炎与抗炎介质的平衡状态，尤其可利用IL-38基因敲除（GKO）小鼠进一步阐明IL-38在介导麝香酮治疗效应中的作用。