Budesonide ameliorates lung injury induced by large volume ventilation.
BACKGROUND
Ventilation-induced lung injury (VILI) is a health problem for patients with acute respiratory dysfunction syndrome. The aim of this study was to investigate the effectiveness of budesonide in treating VILI.


METHODS
Twenty-four rats were randomized to three groups: a ventilation group, ventilation/budesonide group, and sham group were ventilated with 30 ml/kg tidal volume or only anesthesia for 4 hor saline or budesonide airway instillation immediately after ventilation. The PaO2/FiO2and wet-to-dry weight ratios, protein concentration, neutrophil count, and neutrophil elastase levels in bronchoalveolar lavage fluid (BALF) and the levels of inflammation-related factors were examined. Histological evaluation of and apoptosis measurement inthe lung were conducted.


RESULTS
Compared with that in the ventilation group, the PaO2/FiO2 ratio was significantly increased by treatment with budesonide. The lung wet-to-dry weight ratio, total protein, neutrophil elastase level, and neutrophilcount in BALF were decreased in the budesonide group. The BALF and plasma tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, intercellular adhesion molecule (ICAM)-1, and macrophage inflammatory protein (MIP)-2 levels were decreased, whereas the IL-10 level was increased in the budesonide group. The phosphorylated nuclear factor (NF)-kBlevels in lung tissue were inhibited by budesonide. The histological changes in the lung and apoptosis were reduced by budesonide treatment. Bax, caspase-3, and cleaved caspase-3 were down-regulated, and Bcl-2 was up-regulated by budesonide.


CONCLUSIONS
Budesonide ameliorated lung injury induced by large volume ventilation, likely by improving epithelial permeability, decreasing edema, inhibiting local and systemic inflammation, and reducing apoptosis in VILI.
Department of ICU, Cancer Hospital of Harbin Medical University, Harbin, 150081, China.
Ying-Nan
YN
Ju
Department of ICU, Cancer Hospital of Harbin Medical University, Harbin, 150081, China.
Kai-Jiang
KJ
Yu
Department of Anesthesiology, Cancer Hospital of Harbin Medical University, Pain Research Institute of Heilongjiang Academy of Medical Sciences, No. 150 Haping Rd., Nangang District, Harbin, 150081, China. wangguonian609cn@aliyun.com.
Guo-Nian
GN
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D019819:Budesonide / Q000627:therapeutic use*; D053148:Caspase 3 / Q000097:blood / Q000737:chemistry; D054426:Chemokine CXCL2 / Q000097:blood / Q000737:chemistry; D005938:Glucocorticoids / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000737:chemistry; D016753:Interleukin-10 / Q000097:blood / Q000737:chemistry; D053583:Interleukin-1beta / Q000097:blood / Q000737:chemistry; D015850:Interleukin-6 / Q000097:blood / Q000737:chemistry; D007958:Leukocyte Count; D008168:Lung / Q000503:physiopathology*; D008297:Male; D016328:NF-kappa B / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000009:adverse effects*; D013990:Tidal Volume; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000737:chemistry; D055397:Ventilator-Induced Lung Injury / Q000188:drug therapy*; D051028:bcl-2-Associated X Protein / Q000737:chemistry
C494828:Bax protein, rat; D054426:Chemokine CXCL2; C513296:Cxcl2 protein, rat; D005938:Glucocorticoids; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D019819:Budesonide; C505410:Casp3 protein, rat; D053148:Caspase 3
Budesonide; Lung injury; Mechanical ventilation