Role of endothelial nitric oxide synthase in inflammatory response in mice with ventilator-induced lung injury : gene knockout / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of endothelial nitric oxide synthase (eNOS) in inflammatory responses in mice with ventilator-induced lung injury using gene knockout.Methods Twenty-four male C578L/6J wild type mice and 24 male B6.129P2-Nos3tm1Unc/NJU (eNOS gene knockout) mice,aged 10-12 months,weighing 20-25 g,were randomly assigned into 2 groups (n=12 each) using a random number tablesham operation group (group S) and mechanical ventilation group (group MV).The animals were anesthetized with intraperitoneal 1％ pentobarbital sodium 70 mg/kg,and mechanically ventilated after tracheal intubation.The animals were mechanically ventilated for 4 h (oxygen flow rate 0.5 L/min,FiO2 50％,VT 15 ml/kg,RR 70 bpm,PEEP 2 cmH2O).After 4 h of ventilation,blood samples were obtained from the internal carotid artery for detection of PaO2.The animals were then sacrificed and the lungs were removed for determination of wet/dry lung weight (W/D) ratio,myeloperoxidase (MPO) activity,contents of malondialdehyde (MDA),interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α),and pulmonary microvascular permeability,and for microscopic examination of the pathological changes of lung (with electron microscope).Results Compared with group S of wild type mice,PaO2 was significantly decreased,while W/D ratio,MPO activity,contents of MDA,IL-6,TNF-oα and NO,and pulmonary microvascular permeability were increased in MV groups of wild type and gene knockout mice,and no significant change was found in the parameters mentioned above in group S of gene knockout mice.Compared with group MV of wild type mice,PaO2 was significantly increased,while W/D ratio,MPO activity,contents of MDA,IL-6,TNF-α and NO and pulmonary microvascular permeability were decreased in group MV of gene knockout mice.The pathological changes of lung were significantly attenuated in group MV of gene knockout mice as compared with group MV of wild type mice.Conclusion eNOS is involved in inflammatory responses in mice with ventilator-induced lung injury.