OBJECTIVETo investigate the protective effects of different concentrations of ketamine against acute lung injury induced by lipopolysaccharide (LPS) in rats and its mechanism.

METHODSForty-eight male Wistar rats were randomized into 4 equal groups, namely the control group, LPS group, ketamine group I (5 mg/kg), and ketamine group II (10 mg/kg). The neutrophil count, protein contents in the bronchoalveolar lavage fluid (BALF) and the wet/dry lung weight ratio were measured 4 h after LPS injection. TNF-alpha, IL-8, NO, iNOS and NF-kappaB were also measured in the lung tissues.

RESULTSIn LPS group, the neutrophil count, protein contents in BALF, the wet/dry lung weight ratio and the levels of tumor necrosis factor-alpha(TNF-alpha), interleukin-8 (IL-8), and NO were all significantly increased compared with the control group (P<0.01). The mRNA expression of iNOS and the protein expression of NF-kappaB were also increased in LPS groups. Ketamine treatment attenuated the increase in wet/dry lung weight ratio, neutrophil count, and protein contents in BALF in a dose-dependent manner. Ketamine also dose-dependently inhibited the production of TNF-alpha, IL-8 , and NO and lowered iNOS mRNA and NF-kappaB protein expression.

CONCLUSIONKetamine can offer protection against LPS-induced acute lung injury in rats by inhibiting the expression of NF-kappaB and attenuating the production of the inflammatory cytokines.