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IF 4.8 3区医学 Q2 CELL BIOLOGY

Inflammation Research Pub Date : 2025-03-28 DOI:10.1007/s00011-025-02026-3

Liangyong Deng, Qiulei Yu, Gang Kuang, Liuyang Wang, Jing Fan, Lin Ye

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引用次数: 0

摘要

背景：叶黄素具有抗炎作用，但其在脓毒症诱导的急性肝损伤（AHI）中的作用机制尚未阐明。本研究旨在探讨木犀草素对败血症诱导的急性肝损伤的影响和潜在机制：在本研究中，我们利用野生型（WT）小鼠和Toll样受体4（TLR4）缺陷型（TLR4-/-）小鼠以及RAW264.7细胞。我们构建了一个CLP诱导的AHI小鼠模型，以研究木犀草素对小鼠肝脏炎症、存活率和肝脏巨噬细胞亚型的影响。此外，我们还提取了小鼠血清、小鼠骨髓巨噬细胞（BMDMs）和肝组织，并通过流式细胞术、ELISA、Western 印迹（WB）和 qPCR 分析了叶黄素对巨噬细胞极化亚型和下游炎症细胞因子的影响。为了进一步验证木犀草素对巨噬细胞极化的影响并探索其可能的潜在机制，我们使用CLP诱导的AHI小鼠模型和LPS刺激的RAW 264.7巨噬细胞，通过流式细胞术、ELISA、免疫组织化学和Western印迹等方法评估了叶黄素对巨噬细胞极化的影响；细胞培养上清液中TNF-α和IL-10的表达；以及iNOS、ARG-1、NF-κB (P65)、p-P65和MyD88的表达：结果：我们发现木犀草素能减轻肝损伤和炎症反应，提高小鼠的存活率。叶黄素能调节巨噬细胞亚型比例，促进巨噬细胞从促炎的M1表型转变为抗炎的M2表型，减轻体内和体外的炎症反应。此外，木犀草素还能降低 NF-κB (p-P65)、TLR4 和 MyD88 的表达。通过将网络药理学的预测与体内外实验结果相结合，确定了叶黄素缓解败血症诱导的急性肝损伤的机制与 TLR4/MyD88/NF-κB通路密切相关：本研究结果表明，在脓毒症诱导的急性肝损伤中，叶黄素有助于缓解肝损伤，减少促炎细胞因子的表达，促进抗炎因子的表达。这种作用可能与叶黄素通过TLR4/MyD88/NF-κB信号通路调节巨噬细胞极化有关。

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Luteolin modulates liver macrophage subtype polarization and play protective role in sepsis induced acute hepatic injury.

Background: Luteolin has an anti-inflammatory effect, but the mechanism has not been elucidated in sepsis-induced acute hepatic injury (AHI). The purpose of this study was to investigate the effects and potential mechanisms of luteolin on sepsis-induced AHI.

Methods: In this study, we utilized both wild-type (WT) mice and Toll-like receptor 4 (TLR4)-deficient (TLR4^-/-) mice alongside RAW264.7 cells. We constructed a CLP-induced AHI mouse model to study the effects of luteolin on liver inflammation, survival and liver macrophage subtypes in mice. In addition, we extracted mouse serum, mouse bone marrow-derived macrophages (BMDMs) and liver tissue and analysed the effects of luteolin on macrophage polarization subtypes and downstream inflammatory cytokines by flow cytometry, ELISA, Western blotting (WB) and qPCR. To further verify the effect of luteolin on macrophage polarization and explore the possible potential mechanism, we used a CLP-induced AHI mouse model and LPS-stimulated RAW 264.7 macrophages to assess the effect of luteolin on macrophage polarization; the expression of TNF-α and IL-10 in the cell culture supernatant; and the expression of iNOS, ARG-1, NF-κB (P65), p-P65 and MyD88 by flow cytometry, ELISA, immunohistochemistry and Western blotting.

Results: We found that luteolin reduced liver injury and inflammatory response and improved the survival rate of mice. Luteolin modulated the macrophage subtype proportion, promoted the change of macrophages from a proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype, and reduced the inflammatory response both in vivo and in vitro. Moreover, luteolin reduced the expression of NF-κB (p-P65), TLR4 and MyD88. By integrating the predictions from network pharmacology with the in vitro and in vivo experimental results, it was determined that the mechanism by which luteolin alleviates sepsis-induced acute hepatic injury is closely related to the TLR4/MyD88/NF-κB pathway.

Conclusions: The results of this study suggest that luteolin helps alleviate liver injury, reduces the expression of proinflammatory cytokines and promotes the expression of anti-inflammatory factors in sepsis-induced acute hepatic injury. This effect may be related to the regulation of macrophage polarization by luteolin through the TLR4/MyD88/NF-κB signalling pathway.

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来源期刊

Inflammation Research 医学-免疫学

CiteScore

9.90

自引率

1.50%

发文量

134

审稿时长

3-8 weeks

期刊介绍： Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.