Effects of dexmedetomidine-ulinastatin combination on inflammatory responses in lung tissues of endotoxic rats

doi:10.3969/j.issn.1002-1949.2014.04.020

Abstract：Objective To investigate the effects of dexmedetomidine -ulinastatin combination on inflammatory responses in lung tissues of endotoxic rats .Methods Male Wistar rats were randomly divided into five groups: saline control group ( NS group ) was given saline ( 5 mL/kg, iv ) alone;endotoximea group (L group) was given LPS (10 mg/kg, over 10 mins);dexmedetomidine-endotoxin group ( L+D group) was treated identically to the endotoxemic group with the additional administration of dexmedetomidine [ infusion at 1μg/( kg· h) ] immediately after LPS injection;ulinastatin-endotoxin group ( L+U group) was treated identically to the endotoxemic group with the additional administration of ulinastatin (20 000 U/kg, ip) immediately after LPS injection; dexmedetomidine +ulinastatin -endotoxin group ( L +D +U group ) received dexmedetomidine [ infusion at 1 μg/( kg· h ) ] and ulinastatin (20 000 U/kg, ip) immediately after LPS injection .Six hours after LPS or saline injection , rats were sacrificed and the lungs were removed for evaluation of histological characteristics and determination of the cytokine ( TNF-α, IL-1β, IL -6 ) concentrations , myeloperoxidase ( MPO ) activity.The pulmonary expression of intercellular adhesion molecule -1 ( ICAM -1 ) and nuclear factor-κappa B ( NF-κB) p65 was evaluated by immunohistochemistry and Western blotting .Results LPS induced marked lung histological injury and a significant increase in the cytokine ( TNF -α, IL-1β, IL-6) concentrations, myeloperoxidase (MPO) activity in the lung.All these effects were attenuated by dexmedetomidine -ulinastatin combination but not by dexmedetomidine or ulinastatin alone.The expression of ICAM -1 and NF -κB p65 was increased in the L group , and this enhancement of ICAM-1 and NF-κB p65 expression was much less in the L +D+U group but not by L+D or L +U alone.Conclusion Dexmedetomidine -ulinastatin combination inhibits inflammatory reaction in the lung tissues of endotoxic rats by suppressing NF -κB activation.