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麝香草酚通过抑制 LOX-1/IL-1β 信号通路来防治烟曲霉菌角膜炎。

Thymol Protects against Aspergillus Fumigatus Keratitis by Inhibiting the LOX-1/IL-1β Signaling Pathway.

机构信息

Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao, 266003, China.

Department of Otorhinolaryngology-Head and Neck Surgery, the Affiliated Hospital of Qingdao University, Qingdao, 266003, China.

出版信息

Curr Med Sci. 2022 Jun;42(3):620-628. doi: 10.1007/s11596-022-2512-9. Epub 2022 Mar 15.

DOI:10.1007/s11596-022-2512-9
PMID:35292873
Abstract

OBJECTIVE

To explore the anti-inflammatory effects and mechanisms of action of thymol in Aspergillus fumigatus (A. fumigatus) keratitis.

METHODS

The minimum inhibitory concentration of thymol against A. fumigatus was detected. To characterize the anti-inflammatory effects of thymol, mouse corneas and human corneal epithelial cells were pretreated with thymol or dimethyl sulfoxide (DMSO) before infection with A. fumigatus spores. Slit-lamp microscopy, immunohistochemistry, myeloperoxidase detection, quantitative real-time polymerase chain reaction, and Western blotting were used to assess infection. Neutrophil and macrophage recruitment, in addition to the secretion of LOX-1 and IL-1β, were quantified to evaluate the relative contribution of thymol to the inflammatory response.

RESULTS

We confirmed that the growth of A. fumigatus was directly inhibited by thymol. In contrast with the DMSO group, there was a lower degree of inflammation in the mouse corneas of the thymol-pretreated group. This was characterized by significantly lower clinical scores, less inflammatory cell infiltration, and lower expression of LOX-1 and IL-1β. Similarly, in vitro experiments indicated that the production of LOX-1 and IL-1β was significantly inhibited after thymol treatment, in contrast with the DMSO-pretreated group.

CONCLUSION

Our findings demonstrate that thymol exerted a direct fungistatic activity on A. fumigatus. Furthermore, thymol played a protective role in fungal keratitis by inhibiting LOX-1/IL-1β signaling pathway and reducing the recruitment of neutrophils and macrophages.

摘要

目的

探讨麝香草酚对烟曲霉菌(A. fumigatus)角膜炎的抗炎作用及其作用机制。

方法

检测麝香草酚对烟曲霉菌的最小抑菌浓度。为了研究麝香草酚的抗炎作用,在用烟曲霉菌孢子感染前,用麝香草酚或二甲基亚砜(DMSO)预处理小鼠角膜和人角膜上皮细胞。使用裂隙灯显微镜、免疫组织化学、髓过氧化物酶检测、实时定量聚合酶链反应和 Western blot 来评估感染。定量中性粒细胞和巨噬细胞募集以及 LOX-1 和 IL-1β 的分泌,以评估麝香草酚对炎症反应的相对贡献。

结果

我们证实麝香草酚可直接抑制烟曲霉菌的生长。与 DMSO 组相比,麝香草酚预处理组小鼠角膜的炎症程度较低。其特征为临床评分较低,炎症细胞浸润较少,LOX-1 和 IL-1β 的表达较低。同样,体外实验表明,与 DMSO 预处理组相比,麝香草酚处理后 LOX-1 和 IL-1β 的产生明显受到抑制。

结论

我们的研究结果表明,麝香草酚对烟曲霉菌具有直接的抑菌活性。此外,麝香草酚通过抑制 LOX-1/IL-1β 信号通路和减少中性粒细胞和巨噬细胞的募集,在真菌性角膜炎中发挥保护作用。

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本文引用的文献

1
Synthesis and in vitro antibacterial activity of thymol and carvacrol derivatives.百里香酚和香芹酚衍生物的合成及其体外抗菌活性
Acta Pol Pharm. 2010 Jul-Aug;67(4):375-80.
百里香酚通过下调 TLR4/MyD88/NF-κB/IL-1β信号表达,减少坏死性凋亡和焦亡来改善角膜炎。
J Microbiol Biotechnol. 2023 Jan 28;33(1):43-50. doi: 10.4014/jmb.2207.07017. Epub 2022 Dec 1.