基于脂质代谢组学的卵白蛋白诱导小鼠过敏性哮喘机制研究  

Mechanism study of OVA-induced allergic asthma in mice based on lipid metabolomics

作　　者：戎晓娟 孔令霏 康雨彤 秦拓 徐磊 铁偲 RONG Xiao-juan;KONG Ling-fei;KANG Yu-tong;QIN Tuo;XU Lei;TIE Cai(Xinjiang Institute of Material Medica,Urumqi 830004,China;State Key Laboratory of Coal Resources and Safety Mining,Beijing 100083,China)

机构地区：[1]新疆维吾尔自治区药物研究所,新疆乌鲁木齐830004 [2]煤炭资源与安全开采国家重点实验室,北京100083

出　　处：《中国药理学通报》2023年第3期477-483,共7页Chinese Pharmacological Bulletin

基　　金：天山青年计划项目(No 2020Q047);国家自然科学基金项目(No 81960752,81860727);自治区公益性科研院所基本科研业务经费资助项目(No KY2022142)。

摘　　要：目的基于脂质代谢组学研究卵白蛋白(ovalbumin,OVA)诱导小鼠过敏性哮喘的机制,寻找潜在生物标志物。方法建立OVA诱导的BALB/c小鼠过敏性哮喘模型,采用ELISA法测定BALF中TNF-α、IL-4、IL-10、IFN-γ及血清中IgE表达水平;肺组织病理HE染色观察小鼠肺部炎症情况;采用UPLC-MS/MS代谢组学方法研究过敏性哮喘小鼠肺组织及血清中脂质介质变化情况。结果与正常对照组相比较,模型组血清IgE含量明显升高(P<0.05),BALF中TNF-α、IFN-γ含量明显升高(P<0.05);模型组小鼠肺组织可见典型炎症表现;UPLC-MRM共完成57种脂质介质的定量分析,模型组与正常对照组小鼠肺组织和血清中的脂质介质代谢轮廓差异均存在显著性,在肺组织和血清中分别发现17个和6个差异具有显著性的脂质介质,差异性代谢产物通过环氧酶(COX)、脂氧酶(LOX)和细胞色素P450氧化酶(P450)代谢途径产生。结论OVA诱导的过敏性哮喘可引起内源性脂质介质代谢紊乱,与细胞因子相互作用参与哮喘的发生发展,获得的差异性代谢物具有成为表征其发展变化的生物标志物的潜在研究价值。Aim To investigate the mechanism and search for potential biomarkers of ovalbumin(OVA)-induced asthma in mice base on lipidomics.Methods A BALB/c mouse model of asthma was prepared by OVA.TNF-α,IL-4,IL-10,IFN-γlevels in BALF and IgE level in serum were measured by ELISA.The inflammatory changes in mouse lung tissue were observed using HE staining.Lipid mediators(LMs)in lung tissue and serum were quantified with UPLC-MS/MS strategy.Results IgE level in serum and TNF-α,IFN-γlevels in BALF were higher(P<0.05)of asth-matic mice.Typical inflammatory manifestations were seen in lung tissue of asthmatic mice.A total of 57 lipid mediators were quantified with UPLC-MRM.LMs metabolic profiles differed significantly in serum and lung tissue between asthmatic and normal mice,17 significantly different LMs were found in lung tissue and 6 LMs were found in serum,and the differential metabolites were produced through the cyclooxygenase(COX),lipoxygenase(LOX)and cytochrome P450 oxidase(P450)metabolic pathways.Conclusions OVA-induced allergic asthma can cause disorder of lipid mediators,LMs and cytokines are involved in the occurrence and development of asthma.The differential LMs have potential research value as biomarkers for the development of allergic asthma.

关 键 词：过敏性哮喘 脂质介质 类二十烷酸 亚油酸 代谢组学 机制研究 

分 类 号：R332[医药卫生—人体生理学] R322.35[医药卫生—基础医学] R344R364.5R562.25