Losartan Attenuates Ventilator-induced Lung Inj ury by Inhibiting NF-κB in Rats / 华中科技大学学报(医学版)

ABSTRACT

Objective To investigate the protective role of losartan,an angiotensin Ⅱ receptor(AT1 type)blocker,in the mechanical ventilation-induced lung injury(VILI).Methods Forty Sprague-Dawley rats weighing 300-350 g were randomly divided into the following four experimental groups(10 rats in each group)control group(group A),normal tidal volume venti-lation group(group B),large tidal volume mechanical ventilation group(group C),large tidal volume mechanical ventilation plus Losartan pretreatment group(group D).The pulmonary tissues were removed for pathological examination and detection of NF-κB activity,and the lung lavage fluid was collected for analysis of white blood cell count,total protein concentration and the level of MIP-2,after the rats were sacrificed.Results The pathology of lung tissues was normal in groups A and B.There was obvi-ous inflammatory damage in lung tissues in group C.The pathological inj uries of lung tissue were significantly reduced in group D compared with group C.The NF-κB activity and the level of p65 were significantly higher in group C than in groups A and B (P<0.01);they were significantly reduced in group D compared with group C(P<0.05).Total protein concentration,the MIP-2 level and the white blood cell count were significantly higher in group C than in groups A and B(P<0.01).They were significantly reduced in group D compared with group C(P<0.05 or 0.01).Conclusion Losartan,a selective inhibitor of sub-type AT1 receptors for angiotensin Ⅱ,can relieve VILI by inhibiting the activity of NF-κB.