基于斑马鱼炎症模型和原发性中性粒细胞炎症反应的氧化苦参碱对中性粒细胞功能的影响

IF 4.8 2区 医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2024-09-06 DOI:10.1016/j.intimp.2024.113064
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引用次数: 0

摘要

Sophora flavescens Ait.(SFA)是一种广泛用于治疗发烧、炎症、溃疡和与毛刺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,但有关 OMT 所介导的抗炎保护特性和内在机制的研究还不够深入。本研究旨在探索 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。利用斑马鱼这一动物模型具有实时动态观察系统的优势,我们在斑马鱼Tg(mpx:GFP)品系中建立了体内尾鳍伤口模型和硫酸铜诱导炎症模型。结果发现,OMT能明显减弱中性粒细胞的迁移,上调斑马鱼尾鳍伤口模型中受损的JNK、casp3、mapk14a、mapkapk2a和map2k1的mRNA表达水平,下调硫酸铜损伤模型中JNK、casp3、mapk14a、mapkapk2a和map2k1的mRNA表达水平。体外实验表明,OMT 可调节小鼠原代中性粒细胞的趋化反应、增强吞噬能力、降低氧化应激和减轻炎症水平。我们推测,OMT 可能通过 MAPK 信号通路调节原发性中性粒细胞,从而发挥抗炎作用。
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Effect of oxymatrine on neutrophil function based on zebrafish inflammation model and primary neutrophil inflammatory responses

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.

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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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