DOI: 10.1002/ame2.12566
Establishment of rat model for aspiration pneumonia and potential mechanisms
Hanbing Hu
Junfeng Chen
Yiru Shao
Yuedong Tang
Yu Dun
Obulkasim Memet
Xuanrong Bao
Jie Shen
Center of Emergency and Critical Medicine,Jinshan Hospital of Fudan University,Shanghai,China;Research Center for Chemical Injury,Emergency and Critical Medicine of Fudan University,Shanghai,China;Key Laboratory of Chemical Injury,Emergency and Critical Medicine of Shanghai Municipal Health Commission,Shanghai,China
摘要：Background:Aspiration pneumonia is a severe health concern,particularly for ICU patients with impaired airway defenses.Current animal models fail to fully replicate the condition,focusing solely on chemical lung injury from gastric acid while neglecting pathogen-induced inflammation.This gap hinders research on pathogenesis and treatment,creating an urgent need for a clinically relevant model.This study aimed to develop an improved rat model of aspiration pneumonia by combining hydrochloric acid(HCl)and lipopolysaccharide(LPS)administration.
Methods:Specific pathogen-free Sprague Dawley rats underwent intratracheal instillation of HCl and LPS.Techniques included rat weight measurement,tracheal intubation,pulmonary function monitoring,lung tissue sampling with HE staining and scoring,bronchoalveolar lavage fluid(BALF)sampling,protein and inflammatory cytokine analysis via BCA and ELISA,BALF pH determination,Evans Blue dye assessment,blood gas analysis,FITC-dextran leakage,Western blotting,electron microscopy,survival analysis,and transcriptome sequencing with bioinformatics.Statistical analysis was performed using GraphPad Prism.
Results:The optimal model involved instillation of 1.5μL/g.wt HCl(pH=1)followed by 20μg/g.wt LPS after 1 h.This model reproduced acute lung injury,including tissue damage,pulmonary microvascular dysfunction,inflammatory responses,hypoxemia,and impaired pulmonary ventilation,with recovery observed at 72 h.PANoptosis was confirmed,characterized by increased markers.Concentration-dependent effects of HCl and LPS on lung damage were identified,alongside cytokine elevation and microvascular dysfunction.
Conclusions:This optimized model closely mimics clinical aspiration pneumonia,providing a valuable tool for studying pathophysiology and therapeutic strategies.
机标关键词：modelaspirationestablishmentmechanismspneumoniapotential
论文发表日期：2025-06-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：14( 1105-1118 )
英文信息