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用于分析、调节、半定量分析和通路分析的变应性鼻炎小鼠肥大细胞模型中的综合代谢组学

Comprehensive Metabolomics in Mouse Mast Cell Model of Allergic Rhinitis for Profiling, Modulation, Semiquantitative Analysis, and Pathway Analysis.

作者信息

Patil Akshay Suresh, Xu Yan

机构信息

Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA.

出版信息

Biomolecules. 2025 Jan 11;15(1):109. doi: 10.3390/biom15010109.

DOI:10.3390/biom15010109
PMID:39858503
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11763337/
Abstract

Allergic rhinitis affects millions globally, causing significant discomfort and reducing the quality of life. This study investigates the metabolic alterations in murine mast cells (MC/9) under allergic rhinitis conditions induced by lipopolysaccharide (LPS) stimulation, employing UHPLC-QTOF-MS-based untargeted and targeted metabolomics. The analysis identified 44 significantly regulated metabolites, including histamine, leukotrienes, prostaglandins, thromboxanes, and ceramides. Key metabolic pathways such as arachidonic acid, histidine, and sphingolipid metabolisms were notably modulated. The study further examined the therapeutic effects of triprolidine and zileuton, demonstrating their capacity to reverse LPS-induced metabolic shifts. Triprolidine primarily modulated histidine and sphingolipid metabolism, while zileuton targeted arachidonic acid and sphingolipid metabolism. These findings underscore the utility of metabolomics analysis in elucidating the complex biochemical pathways involved in allergic rhinitis and highlight the potential of metabolomics for evaluating therapeutic interventions. This study enhances our understanding of mast cell metabolism in allergic responses and provides a robust model for assessing the efficacy of anti-allergic agents, paving the way for more effective treatments.

摘要

过敏性鼻炎在全球范围内影响着数百万人,造成极大不适并降低生活质量。本研究利用基于超高效液相色谱-四极杆飞行时间质谱(UHPLC-QTOF-MS)的非靶向和靶向代谢组学技术,调查脂多糖(LPS)刺激诱导的过敏性鼻炎条件下小鼠肥大细胞(MC/9)的代谢变化。分析确定了44种显著调节的代谢物,包括组胺、白三烯、前列腺素、血栓素和神经酰胺。花生四烯酸、组氨酸和鞘脂代谢等关键代谢途径受到显著调节。该研究进一步考察了曲普利啶和齐留通的治疗效果,证明它们有能力逆转LPS诱导的代谢变化。曲普利啶主要调节组氨酸和鞘脂代谢,而齐留通则针对花生四烯酸和鞘脂代谢。这些发现强调了代谢组学分析在阐明过敏性鼻炎所涉及的复杂生化途径方面的实用性,并突出了代谢组学在评估治疗干预措施方面的潜力。本研究增进了我们对过敏反应中肥大细胞代谢的理解,并为评估抗过敏药物的疗效提供了一个有力的模型,为更有效的治疗铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/4e5de6c07d2d/biomolecules-15-00109-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/64302a2b31b9/biomolecules-15-00109-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/a5997fe5d218/biomolecules-15-00109-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/e659e96392d1/biomolecules-15-00109-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/771bdf5da029/biomolecules-15-00109-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/88a57b0c4a4b/biomolecules-15-00109-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/4e5de6c07d2d/biomolecules-15-00109-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/64302a2b31b9/biomolecules-15-00109-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/a5997fe5d218/biomolecules-15-00109-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/e659e96392d1/biomolecules-15-00109-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/771bdf5da029/biomolecules-15-00109-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/88a57b0c4a4b/biomolecules-15-00109-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c0/11763337/4e5de6c07d2d/biomolecules-15-00109-g006.jpg

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