Role And Mechanism Of Angiotensin ? Receptor Blocker In Lung Injury Induced By One Lung Ventilation

BackgroundOne lung ventilation(OLV)is a ventilation method that relies on the use of double lumen endotracheal intubation to ventilate one lung while the other lung collapses due to passive deflation.However,in the process of one lung ventilation,pulmonary devascularization and resuscitation can increase the incidence of postoperative acute lung injury(ALI).Lung damage caused by ALI is the main cause of death after thoracic surgery.So far,the mechanism of lung injury during one lung ventilation has not been fully clarified.Existing studies have found that angiotensin ? receptor blocker(ARB)has the effects of anti-inflammatory and reducing oxidative stress,which is closely related to organ ischemia-reperfusion injury.Growth differentiation factor-15(GDF-15)is a stress reactive cytokine,and its level is elevated in diseases such as acute respiratory distress syndrome,heart failure and acute coronary syndrome.However,the role of ARB and GDF-15 in lung injury during one lung ventilation is not clear.Therefore,this study intends to explore the role and mechanism of ARB and GDF-15 in lung injury during one lung ventilation.ObjectivesThe genomic changes of lung tissue after one lung ventilation were observed by translatomics and transcriptomics to explore the mechanism of lung injury.Clarify the mechanism of the protective effect of ARB and GDF-15 on lung injury caused by one lung ventilation.MethodsSprague Dawley rats were used to make one lung ventilation model.ARB and one lung ventilation intervention were given.The protective effect of ARB on lung injury was evaluated from three aspects:inflammatory response,oxidative stress and permeability changes by HE staining,immunohistochemistry and ELISA.Human umbilical vein endothelial cells(HUVECs)and human type II lung epithelial cells(A549)were used to make the lung injury model of air break and resuscitation in vitro.ARB and hypoxia reoxygenation intervention were given.The protective effect of ARB on cell hypoxia reoxygenation injury was evaluated from three aspects:inflammatory response,oxidative stress and permeability change by ELISA,cell flow cytometry and confocal immunofluorescence.ResultsThe results of pathological injury score of lung tissue,ELISA and immunohistochemistry showed that the injury score of lung injury group with one lung ventilation increased significantly(P<0.0005),and the levels of inflammatory factors,oxidative stress and tissue permeability increased significantly.In vitro,the results of confocal immunofluorescence,ELISA and fluorescence leakage suggest that at the cellular level,the levels of inflammatory factors,oxidative stress and tissue permeability in hypoxia reoxygenation group increased significantly.Then,we performed translatomics and transcriptomics analysis on rat lung tissue and found that RAS system changed significantly during one lung ventilation.Combined with histological analysis,pre-treatment with ARB can reduce the degree of lung injury caused by one lung ventilation.Through the results of previous experimental studies,further study the role of GDF-15 in lung injury caused by one lung ventilation.The expression of GDF-15 in lung tissue in one lung ventilation group was up-regulated,and the expression level of GDF-15 was further up-regulated after ARB treatment.After interfering with the expression of GDF-15,it was found that the protective effect of ARB was lost.ConclusionsOne lung ventilation model can lead to acute lung injury.ARB reduces the degree of one lung ventilation lung injury by up regulating the expression level of GDF-15.