Early administration of propofol protects against endotoxin-induced acute lung injury in rats by inhibiting the TGF-beta1-Smad2 dependent pathway.
OBJECTIVE
To assess the effects of propofol treatments at different time points on acute lung injury and on the expression of transforming growth factor (TGF)-beta1 and the downstream target of TGF-beta1, Smad 2, in the lung tissues in the endotoxic rats.


METHODS
Seventy-six Wistar rats were randomly assigned to five groups: control group (saline only), endotoxemic group [lipopolysaccharide (LPS) 8 mg kg(-1), i.v.], and three propofol-treated groups. For the propofol-treated groups, propofol (5 mg kg(-1), i.v. bolus) was administered either 1 h before LPS, simultaneously with LPS, and 1 h after LPS, and all were followed by infusion of 10 mg kg(-1) h(-1) of propofol for 5 h after LPS. Lung tissues were sampled to measure myeloperoxidase activity and expression of TGF-beta1 and Smad2 and to assess pulmonary microvascular permeability and histopathological changes.


RESULTS
The hemodynamics, arterial blood gases, 5 h survival rate, pulmonary microvascular permeability, and acute lung injury scores were significantly better, and expression of TGF-beta1 and Smad2 and myeloperoxidase activity in lung tissues was significantly lower in the pretreatment and simultaneous treatment groups compared to the endotoxemic group. However, there were no significant differences in all observed variables between the endotoxemic and postreatment groups. Except for TGF-beta1 expression in lung tissues, the other observed variables were also not significantly different between the pretreatment and simultaneous treatment groups.


CONCLUSIONS
In the endotoxic rat model, pretreatment and simultaneous treatment with propofol provided protection against acute lung injury by inhibiting the TGF-beta1-Smad2 dependent pathway.
Gao
Ju
J
Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Jiangsu, China. gaoju_003@163.com [corrected]
Zhao
Wei-Xian
WX
Xue
Fu-Shan
FS
Zhou
Luo-Jing
LJ
Xu
Shao-qun
SQ
Ding
Ning
N
D055371:Acute Lung Injury / Q000378:metabolism / Q000517:prevention & control; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D018686:Anesthetics, Intravenous; D008070:Lipopolysaccharides; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D053773:Transforming Growth Factor beta1; D009195:Peroxidase; D015742:Propofol