NF-κB信号通路在低分子量多环芳烃致肺部炎症中的作用机制研究

Mechanism behind of the action of NF-κB signaling pathway in pulmonary inflammation caused by low molecular weight polycyclic aromatic hydrocarbons

摘要

目的 探讨低分子量多环芳烃（LMW-PAHs）通过氧化应激激活核因子κB（NF-κB）、磷酸化核因子κB(p-NF-κB)信号通路诱导肺部炎性损伤的作用机制。方法 建立 LMW-PAHs 染毒动物模型并观察大鼠肺组织的病理学变化，检测肺部炎症因子白介素-1β（IL-1β）和 IL-4的蛋白表达水平，氧化应激指标谷胱甘肽过氧化物酶和总抗氧化能力以及NF-κB信号通路蛋白表达水平，探讨 LMW-PAHs 造成肺部炎症的机制。结果 各染毒组与对照组比较，谷胱甘肽过氧化物酶活性和总抗氧化能力浓度均降低 (P<0.05);NF-κB/p-NF-κB蛋白活性显著增高 (P<0.05) ；高剂量组 IL-1β水平显著增高 (P<0.05)；各剂量组 IL-4 水平显著降低 (P<0.05)。结论 LMW-PAHs 可引起氧化应激进而激活 NF-κB信号通路促进炎症因子释放，对肺部造成炎性损伤。

Abstract

Objective To investigate the mechanism by which low molecular weight polycyclic aromatic hydrocarbons（LMW-PAHs）induce pulmonary inflammatory injury through the activation of the nuclear fac- tor kappa-B（NF-κB）/phosphorylation nuclear factorκB(p-NF-κB)signaling pathway via oxidative stress．Methods An LMW-PAHs-exposed animal model was established．Pathological changes in rat lung tissue were observed．Protein expression levels of pulmonary inflammatory mediators interleukin-1β（IL-1β）and IL-4 were detected．The oxidative stress markers glutathione peroxidase（GSH-PX）and total antioxidant capacity （T-AOC），and the expression levels of NF-κB signaling pathway proteins were observed to investigate the mechanisms by which LMW-PAHs induce pulmonary inflammation．Results Compared with the control group，all exposed groups showed decreased T-AOC concentration and GSH-PX activity（P<0.05）；NF-κB/p-NF-κB protein activity was significantly elevated（P<0.05）；IL-1β levels were significantly increased in the high-dose group（P<0.05）；IL-4 levels were significantly reduced across all dose groups（P<0.05）．Conclusion LMW-PAHs induce oxidative stress，thereby activating the NF-κB signaling pathway to promote inflammatory cytokine release，thus resulting in inflammatory lung injury．

关键词

低分子量多环芳烃 / 炎症 / 氧化应激 / 核因子 κB 信号通路 / 磷酸化核因子 κB 信号通路 / 肺炎 / 机制

Key words

low molecular weight polycyclic aromatic hydrocarbons / inflammation / oxidative stress / nuclear factor kappa-B signaling pathway / phosphorylation nuclear factorκB signaling pathway / pulmonary inflam- mation / mechanism

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基金资助

中央高校项目＂青稞计划＂资助项目(lzujbky-2024-it67)

中央高校项目＂青稞计划＂资助项目(lzujbky-2024-it21)

甘肃省科技重点研发计划资助项目(25YF- FA028)

2025年国家级大学生创新创业训练计划资助项目(20250080023)