[Pathogenic role leukotriene B4 in lung injury induced by lung-protective mechanical ventilation in rabbits].

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Tytuł:: [Pathogenic role leukotriene B4 in lung injury induced by lung-protective mechanical ventilation in rabbits].
Autorzy:: Yuan L; Department of Anesthesiology, Third People's Hospital of Yunnan Province, Kunming 650011, China.
Li J; Department of Anesthesiology, First People's Hospital of Yunnan Province, Kunming 650032, China.
Yang Y; Experimental Center of Medical Function, Kunming Medical University, Kunming 650500, China.
Guo X; Department of Anesthesiology, First People's Hospital of Yunnan Province, Kunming 650032, China.
Liu X; Department of Anesthesiology, First People's Hospital of Yunnan Province, Kunming 650032, China.
Li L; Department of Anesthesiology, First People's Hospital of Yunnan Province, Kunming 650032, China.
Zhu X; Department of Anesthesiology, First People's Hospital of Yunnan Province, Kunming 650032, China.
Liu R; Department of Anesthesiology, First People's Hospital of Yunnan Province, Kunming 650032, China.
Źródło:: Nan fang yi ke da xue xue bao = Journal of Southern Medical University [Nan Fang Yi Ke Da Xue Xue Bao] 2020 Oct 30; Vol. 40 (10), pp. 1465-1471.
Typ publikacji:: Journal Article
Język:: Chinese
Imprint Name(s):: Original Publication: Guangzhou : Nanfang yi ke da xue xue bao bian ji bu, 2005-
MeSH Terms:: Lung Injury*/etiology
Lung Injury*/prevention & control
Animals ; Bronchoalveolar Lavage Fluid ; Leukotriene B4 ; Lung ; Neutrophils ; Rabbits ; Respiration, Artificial/adverse effects
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Contributed Indexing:: Keywords: AMP/Rap1 signaling pathway; bestatin; cAMP/protein kinase A signaling pathway; leukotriene B4; lung injury; mechanical ventilation
Substance Nomenclature:: 1HGW4DR56D (Leukotriene B4)
Entry Date(s):: Date Created: 20201029 Date Completed: 20201102 Latest Revision: 20220902
Update Code:: 20240105
PubMed Central ID:: PMC7606227
DOI:: 10.12122/j.issn.1673-4254.2020.10.12
PMID:: 33118515
: Czasopismo naukowe

Objective: To elucidate the pathogenic role of leukotriene B4 (LTB4) in pulmonary hyper-permeability and inflammation induced by lung-protective mechanical ventilation (LPMV) in rabbits.
Methods: Thirty-two healthy Japanese white rabbits were randomized into 4 groups for treatment with vehicle or bestatin (a leukotriene A4 hydrolase inhibitor that inhibits LTB4 production) administered intragastrically at the daily dose of 8 mg/kg for 5 days, followed by sham operation (group S and group BS, respectively, in which the rabbits were anesthetized only) or LPMV (group PM and group BPM, respectively, in which the rabbits received ventilation with 50% oxygen at a tidal volume of 8 mL/kg for 5 h). The concentrations of LTB4 and cyclic adenosine monophosphate (cAMP) in the lung tissues were analyzed by ELISA. cAMP content, protein kinase A (PKA) protein expression and the Rap1-GTP protein to total Rap1 protein ratio were determined to assess the activities of cAMP/PKA and Rap1 signaling pathways. The lung injury was evaluated by assessing lung permeability index, lung wet/dry weight ratio, polymorphonuclear leukocyte (PMN) count in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity and lung histological scores.
Results: None of the examined parameters differed significantly between group S and group BS. All the parameters with the exception of lung histological score increased significantly in group PM and group BPM as compared to those in group S ( P < 0.05). Compared with those in PM group, the rabbits in group BPM showed significantly reduced LTB4 production in the lungs ( P < 0.05), up-regulated cAMP/ PKA and Rap1 signaling pathway activities ( P < 0.05), and alleviated lung hyper-permeability and inflammation ( P < 0.05).
Conclusions: LPMV can induce LTB4 overproduction to down-regulate cAMP/PKA and Rap1 signaling pathways in the lungs of rabbits, which results in lung hyper-permeability and inflammation. Bestatin can inhibit LTB4 production in the lungs to protect against LPMV-induced lung hyper-permeability and inflammation.

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