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基于MEK/ERK通路探讨清热解毒扶正方调控中性粒细胞胞外诱捕网治疗肺炎的机制

郑旭丹 徐菁菁 梅雪 孙肖 赵鹏 孙颖 田燕歌

中国比较医学杂志2026,Vol.36Issue(11):33-45,13.
中国比较医学杂志2026,Vol.36Issue(11):33-45,13.DOI:10.3969/j.issn.1671-7856.2026.11.004

基于MEK/ERK通路探讨清热解毒扶正方调控中性粒细胞胞外诱捕网治疗肺炎的机制

Mechanism of a Heat-Clearing,Detoxifying,and Supporting Formula in treating pneumonia by regulating neutrophil extracellular traps through MEK/ERK signaling

郑旭丹 1徐菁菁 1梅雪 1孙肖 1赵鹏 2孙颖 1田燕歌2

作者信息

  • 1. 河南中医药大学医学院,郑州 450046
  • 2. 河南中医药大学呼吸疾病中医药防治省部共建协同创新中心,河南省中医药防治呼吸病重点实验室,郑州 450046
  • 折叠

摘要

Abstract

Objective The mechanism by which the Heat-Clearing,Detoxifying,and Supporting Formula-Toxin-Clearing Formula inhibits mitogenactivated proteinkinase kinase(MEK)/extracellular signal-regulated kinase(ERK)signaling to regulate neutrophil extracellular traps(NET)formation and alleviate pneumonia.Methods Tracheal drip injection of Klebsiella pneumoniae was used to establish a mouse model of pneumonia.Mice were divided into blank control,model,ceftriaxone,and low-and high-dose DSQ groups.The pharmacodynamic effects of Toxin-Clearing Formula on mice with pneumonia were evaluated by assessing general condition,alveolar lavage fluid cell count,and lung pathology.Myeloperoxidase(MPO)activityin lung tissues was detected with a colorimetric assay kit.The protein levels of tumor necrosis factor(TNF)-α and interleukin(IL)-6 in lung homogenates were quantified using ELISA and quantitative reverse-transcription PCR was used to detect TNF-α,IL-6,IL-1β,lymphocyte antigen 6 complex,locus G(Ly6G),MPO,neutrophil elastase(NE),citrullinated histone H3(Cit-H3),and peptide arginine deaminase 4(PAD4)mRNA expression in lung tissues.Immunohistochemistry(IHC)was used to observe Ly6G,MPO,NE,and Cit-H3 expression in lung tissue sections,while immunofluorescence(IF)was used to observe NET expression.Western blot analysis was used to detect MEK,P-MEK,ERK,P-ERK,PAD4,and Cit-H3 protein expression in lung tissues.Results Toxin-Clearing Formula significantly improved symptoms such as shortness of breath and weight loss in mice with pneumonia,reduced inflammatory cell infiltration in lung tissue,and decreased MPO activity and TNF-α and IL-6 levels(P<0.05,P<0.01).mRNA and protein expression of Ly6G,MPO,NE,Cit-H3,and PAD4 were reduced(P<0.05,P<0.01),NET formation was inhibited,and the phosphorylation level of the MEK/ERK pathway was decreased(P<0.05,P<0.01).Conclusions Toxin-Clearing Formula may alleviate pneumonia by inhibiting the MEK/ERK pathway and reducing NET formation.

关键词

肺炎/中性粒细胞胞外诱捕网/毒素清/MEK/ERK通路

Key words

pneumonia/neutrophil extracellular trapping network/Toxin-Clearing Formula/MEK/ERK pathway

分类

医药卫生

引用本文复制引用

郑旭丹,徐菁菁,梅雪,孙肖,赵鹏,孙颖,田燕歌..基于MEK/ERK通路探讨清热解毒扶正方调控中性粒细胞胞外诱捕网治疗肺炎的机制[J].中国比较医学杂志,2026,36(11):33-45,13.

基金项目

河南省自然科学基金(242300421294). (242300421294)

中国比较医学杂志

1671-7856

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