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METRNL通过IKK/IκB/NF-κB信号通路减轻卵清蛋白/脂多糖诱导的过敏性气道疾病中的氧化应激和炎症缺陷。

METRNL mitigates oxidative stress and inflammatory drawbacks in ovalbumin/lipopolysaccharide-induced allergic airway diseases via the IKK/IκB/NF-κB signaling pathway.

作者信息

Khodir Suzan A, Shaban Anwaar M, Sweed Eman, El-Aziz Noha M Abd, Mostafa Basma Abdelnaby, Latif Asmaa A Abdel, El-Kalshy Mai M, Elgizawy Eman I

机构信息

Medical Physiology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt.

Medical Physiology Department, Menoufia National University, Menoufia, Egypt.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 17. doi: 10.1007/s00210-025-04070-6.

DOI:10.1007/s00210-025-04070-6
PMID:40244452
Abstract

This study aimed to examine the potential impacts of METRNL as an antioxidant and anti-inflammatory through IκB kinase/inhibitor of nuclear factor-kappa B/nuclear factor-kappa-light-chain signaling pathway on many biomarkers and lung structure in rats with bronchial asthma induced by ovalbumin/lipopolysaccharide (OVA/LPS). Forty rats were randomly divided into four equal groups: control group, vehicle group, diseased (OVA/LPS) group OVA 2.5 ml/kg intratracheal installation/LPS 1.5 mg/kg intraperitoneally, and treated (OVA/LPS + METRNL) group, METRNL at a dose of 2 mg/rat/day IV. After 4 weeks, plasma and lung tissues were analyzed to assess oxidative stress inflammatory markers. Additionally, a histological assessment was conducted on lung tissues. Bronchial asthma was confirmed when increased levels of total serum IgE, total cell count, neutrophils, eosinophils, macrophages, and lymphocyte counts in the BAL fluid were observed. Moreover, OVA/LPS resulted in a reduction in levels of superoxide dismutase (SOD) while raising levels of malondialdehyde (MDA). Furthermore, it elevated concentrations of plasma inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin 17 (IL-17), and transforming growth factor beta (TGF-β). The protective effects of METRNL were analyzed. The observed impacts are believed to result from the drug's anti-inflammatory and antioxidant properties and its action on the IKK/IκB/NF-κB signaling pathway. This investigation indicates that METRNL treatment positively improved rats' biochemical and histological aspects of OVA/LPS-induced airway allergic inflammation.

摘要

本研究旨在通过IκB激酶/核因子-κB抑制剂/核因子-κB轻链信号通路,研究METRNL作为抗氧化剂和抗炎剂对卵清蛋白/脂多糖(OVA/LPS)诱导的支气管哮喘大鼠多种生物标志物和肺结构的潜在影响。40只大鼠随机分为四组,每组10只:对照组、赋形剂组、疾病(OVA/LPS)组(经气管内注入OVA 2.5 ml/kg/腹腔注射LPS 1.5 mg/kg)和治疗(OVA/LPS + METRNL)组(以2 mg/大鼠/天的剂量静脉注射METRNL)。4周后,分析血浆和肺组织以评估氧化应激炎症标志物。此外,对肺组织进行了组织学评估。当观察到血清总IgE、总细胞计数、中性粒细胞、嗜酸性粒细胞、巨噬细胞和BAL液中淋巴细胞计数增加时,确诊为支气管哮喘。此外,OVA/LPS导致超氧化物歧化酶(SOD)水平降低,同时丙二醛(MDA)水平升高。此外,它还提高了血浆炎症介质的浓度,包括肿瘤坏死因子-α(TNF-α)、白细胞介素17(IL-17)和转化生长因子-β(TGF-β)。分析了METRNL的保护作用。据信,观察到的影响是由于该药物的抗炎和抗氧化特性及其对IKK/IκB/NF-κB信号通路的作用。本研究表明,METRNL治疗对OVA/LPS诱导的气道过敏性炎症大鼠的生化和组织学方面有积极改善作用。

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Allergy. 2025 Feb;80(2):474-488. doi: 10.1111/all.16150. Epub 2024 May 10.
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The Function and Mechanism of Anti-Inflammatory Factor Metrnl Prevents the Progression of Inflammatory-Mediated Pathological Bone Osteolytic Diseases.抗炎因子Metrnl预防炎症介导的病理性骨溶解疾病进展的功能及机制
J Inflamm Res. 2024 Mar 11;17:1607-1619. doi: 10.2147/JIR.S455790. eCollection 2024.
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Protective role of the novel cytokine Metrnl/ interleukin-41 in host immunity defense during sepsis by promoting macrophage recruitment and modulating Treg/Th17 immune cell balance.
新型细胞因子 Metrnl/白细胞介素-41 通过促进巨噬细胞募集和调节 Treg/Th17 免疫细胞平衡,在脓毒症宿主免疫防御中发挥保护作用。
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Meteorin-like/Metrnl, a novel secreted protein implicated in inflammation, immunology, and metabolism: A comprehensive review of preclinical and clinical studies.类流星蛋白/Metrnl,一种新型分泌蛋白,涉及炎症、免疫学和代谢:临床前和临床研究的全面综述。
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