Dexamethasone attenuated endotoxin-induced acute lung injury through inhibiting expression of inducible nitric oxide synthase.
Application of glucocorticoids in sepsis or severe infection is disputable in clinic. In this experiment, we studied the effect of dexamethasone on nitric oxide synthases and whether dexamethasone could attenuate endotoxin-induced acute lung injury (ALI). SD rats received 5 mg/kg lipopolisaccharide (LPS) injection. Then arterial oxygen partial pressure (PaO2), lung histology, lung tissue nitric oxide (NO) production and expression of nitric oxide synthases (NOS) were detected at 0.5, 1, 2, 3 or 4 h after LPS injection. PaO2 and lung injury deteriorated upon time. Production of NO in lung tissue increased significantly particularly in the first two hours, and this change was mainly due to the over-expression of inducible NOS (iNOS), but not endothelial NOS (eNOS). Furthermore, a tight positive correlation was observed between lung injury score (LIS) and NO production level in lung tissue. Dexamethasone could ameliorate PaO2 and lung damage evidently, which were paralleled by significant decreases in the production of NO and in the expression of iNOS mRNA. In conclusion, dexamethasone could effectively attenuate endotoxin-induced lung injury through inhibiting iNOS expression and activation in the very early stage of ALI.
Yu
Zhui
Z
Intensive Care Unit, Zhongnan Hospital of Wuhan University, 430071 Wuhan, China.
Ouyang
Jing-Ping
JP
Li
Yin-Ping
YP
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000201:enzymology; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D008070:Lipopolysaccharides; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000201:enzymology
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D003907:Dexamethasone; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen