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氧化苦参碱基于斑马鱼炎症模型和原代中性粒细胞炎症反应对中性粒细胞功能的影响。

Effect of oxymatrine on neutrophil function based on zebrafish inflammation model and primary neutrophil inflammatory responses.

机构信息

State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China.

State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China; Department of Pharmacy, Guizhou Provincial People's Hospital, No.83 Zhongshandong Road, Guiyang, Guizhou Province, China.

出版信息

Int Immunopharmacol. 2024 Dec 5;142(Pt A):113064. doi: 10.1016/j.intimp.2024.113064. Epub 2024 Sep 6.

Abstract

Sophora flavescens Ait. (SFA), an extensively utilized herb for the treatment of fevers, inflammatory disorders, ulcers and skin diseases related to bur, contains oxymatrine (OMT) as its principal active constituent. OMT exerts regulatory effects over inflammation, oxidative stress and apoptosis. Neutrophils, critical regulators of the inflammation response, have not been thoroughly elucidated regarding the protective properties and underlying mechanisms of OMT-mediated anti-inflammation. This study was aim to explore the protective effect of OMT on neutrophils under inflammatory conditions and delve into its potential mechanism. Leveraging the advantages of zebrafish, an animal model with a real-time dynamic observation system, we established an in vivo caudal fin wound model and a copper sulfate induced-inflammation model in zebrafish line Tg (mpx:GFP). The result revealed that OMT significantly attenuated neutrophil migration, upregulated the mRNA expression levels of JNK, casp3, mapk14a, mapkapk2a and map2k1 damaged by zebrafish caudal fin wound model, and downregulated mRNA expression levels of JNK, casp3, mapk14a, mapkapk2a and map2k1 in the copper sulfate injury model. In vitro experiments demonstrated that OMT modulated the chemotaxis response of primary neutrophils from mice, enhanced phagocytosis, reduced oxidative stress and alleviated inflammation level. We hypothesize that the OMT may exert its anti-inflammatory effects by regulating primary neutrophils through the MAPK signaling pathway.

摘要

苦参(SFA)是一种广泛用于治疗发热、炎症性疾病、溃疡和与烧伤有关的皮肤病的草药,其主要活性成分为氧化苦参碱(OMT)。OMT 对炎症、氧化应激和细胞凋亡具有调节作用。中性粒细胞是炎症反应的关键调节因子,但关于 OMT 介导的抗炎作用的保护特性和潜在机制尚未得到充分阐明。本研究旨在探讨 OMT 在炎症条件下对中性粒细胞的保护作用,并深入研究其潜在机制。利用具有实时动态观察系统的动物模型斑马鱼的优势,我们建立了斑马鱼尾部 fin 伤口模型和硫酸铜诱导炎症模型 Tg(mpx:GFP)。结果表明,OMT 显著抑制了中性粒细胞的迁移,上调了斑马鱼尾部 fin 伤口模型中 JNK、casp3、mapk14a、mapkapk2a 和 map2k1 的 mRNA 表达水平,并下调了硫酸铜损伤模型中 JNK、casp3、mapk14a、mapkapk2a 和 map2k1 的 mRNA 表达水平。体外实验表明,OMT 调节了来自小鼠的原代中性粒细胞的趋化反应,增强了吞噬作用,减轻了氧化应激并降低了炎症水平。我们假设 OMT 可能通过调节 MAPK 信号通路对原代中性粒细胞发挥抗炎作用。

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