Inhibition of leukotriene-mediated inflammatory response improves acute lung injury and bronchopulmonary dysplasia in neonatal rats
Objective:To explore the therapeutic effect of anti-leukotriene drugs zileuton and montelukast on lipopolysaccharide(LPS)induced acute lung injury(ALI)and bronchopulmonary dysplasia(BPD)in neonatal rats.Methods:The newborn rats were divided into the control group,the dimethyl sulfoxide(DMSO)group,the LPS model group,the LPS+montelukast group,and the LPS+zileuton group.The control group was given 0.9%NaCl and DMSO after normal newborn Wistar rats were delivered;the model group was intraperitoneally injected with LPS(2.5 mg/kg)on the 20th and 21st days of pregnancy for consecutive two days,and the intervention group was given montelukast and zileuton at 10 mg/kg intraperitoneally every other day after the delivery of the model rats until postna-tal day 14.The pathological changes of lung tissue of rats in each group within 24 hours of birth,7 days,and 14 days after birth were observed,and the expression of leukotriene synthase 5-lipoxygenase(5-LO)and leukotriene receptor 1(CysLTR1)in lung tissue was detected.Also,the content of the LTB4,cytokine IL-1β,IL-6,and TNF-α in alveolar lavage fluid was detected.Results:The ALI and BPD models of rats were successfully constructed.It was observed that the expression of 5-LO and CysLTR1 mRNA and protein in the lung tissues of ALI and BPD rats increased,and LTB4 and pro-inflammatory factors IL-1β,IL-6,and TNF-α in alveolar lavage fluid increased too.The expres-sion of 5-LO in the zileuton group decreased and the content of LTB4,IL-1β,IL-6,and TNF-α de-creased too.No difference was found in the expression of CysLTR1 and the content of LTB4 be-tween the montelukast group and the model group,while the contents of IL-1β,IL-6,and TNF-α de-creased in the montelukast group.The pathological changes of lung tissue in the zileuton and montelu-kast groups improved.Conclusion:Anti-leukotriene drugs montelukast and zileuton may improve symptoms of acute lung injury and bronchopulmonary dysplasia in newborn rats.
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