Pathogenic role leukotriene B4 in lung injury induced by lung-protective mechanical ventilation in rabbits.
10.12122/j.issn.1673-4254.2020.10.12
- Author:
Lingyue YUAN
1
;
Jiang LI
2
;
Yong YANG
3
;
Xin GUO
2
;
Xingling LIU
2
;
Lisha LI
2
;
Xiaoyan ZHU
2
;
Rui LIU
2
Author Information
1. Department of Anesthesiology, Third People's Hospital of Yunnan Province, Kunming 650011, China.
2. Department of Anesthesiology, First People's Hospital of Yunnan Province, Kunming 650032, China.
3. Experimental Center of Medical Function, Kunming Medical University, Kunming 650500, China.
- Publication Type:Journal Article
- Keywords:
AMP/Rap1 signaling pathway;
bestatin;
cAMP/protein kinase A signaling pathway;
leukotriene B4;
lung injury;
mechanical ventilation
- MeSH:
Animals;
Bronchoalveolar Lavage Fluid;
Leukotriene B4;
Lung;
Lung Injury/prevention & control*;
Neutrophils;
Rabbits;
Respiration, Artificial/adverse effects*
- From:
Journal of Southern Medical University
2020;40(10):1465-1471
- CountryChina
- Language:Chinese
-
Abstract:
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 (
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.
