SDF-1?/CXCR4 Signaling Modulation Improves The Therapeutic Effect Of Bone Marrow Mesenchymal Stem Cells On Seawater Drowning Induced Acute Lung Injury In Rats

With the development of marine transportation,marine tourism and marine aquaculture,as well as the marine training and exercises conducted by the armed forces,the number of people drowned by sea increases year by year.Because seawater is hypertonic,alkaline,and contains multiple pathogens,the damage from drowning in seawater is usually more severe than in fresh water.In recent years,more and more attention has been paid to acute lung injury(ALI)related to seawater drowning.After seawater drowning,it first damages the lung parenchymal cells.On the other hand,it starts the acute inflammatory reaction,leading to seawater drowning induced acutelung injury(SWD-ALI),which is obviously more severe than other types of lung injury,and can rapidly develop into seawater respiratory distress syndrome(SW-RDS).Early etiological treatment,symptomatic support and respiratory support are the common treatment options at present.Seawater drowning acute lung injury is a dangerous disease.Despite the improvement of diagnosis and treatment equipment,the mortality rate of SW-RDS is still at a high level.Studies have shown that bone marrow mesenchymal stem cells repair tissue damage.In recent years,bone marrow mesenchymal stem cells(BMSCs)have been used in many experimental studies and have been used to treat lung injury and various respiratory diseases with initial results.The purpose of this study was to observe the regulatory effect of SDF-1?/CXCR4 signaling pathway on bone marrow mesenchymal stem cells in the treatment of seawater inhalation lung injury,and to investigate its mechanism.BMSCs of rats were collected by whole bone marrow adherent culture.BMSCs phenotype was identified by flow cytometry and osteoblast differentiation was induced.The effect of SDF-1? / CXCR4 blocker AMD3100 on BMSCs migration was investigated by Transwells.SDF-1?/CXCR4 signal in the treatment SW-RDS by exogenous BMSCs transplantation was evaluated in terms of lung tissue wet/dry weight ratio,pathological changes,mRNA expression and protein levels of SDF-1? /CXCR4.ObjectiveTo investigate the effects of bone marrow mesenchymal stem cells(BMSCs)on the repair of seawater inhalation lung injury and SDF-1? /CXCR4 signaling.MethodsSD rats were isolated and cultured for BMSCs,and a rat model of seawater inhalation lung injury was established.BMSCs migration was detected by Transwelll assay,BMSCs and SDF-1?/CXCR4 signals were pretreated with CXCR4 blocker AMD3100,SDF-1?/CXCR4 signals were regulated by lung administration,SDF-1?/CXCR4 expressions were detected by real-time PCR and Western blot,lung injury was detected by HE staining and lung wet-dry ratio.ResultsIn vitro Transwell assay showed that SDF-1? promoted the migration of BMSCs,which was antagonistic to AMD3100.BMSCs improved lung tissue exudation,edema and inflammatory cell infiltration induced by seawater inhalation,and reduced lung wet-to-dry ratio.Pretreatment with AMD3100 inhibited the above therapeutic effect of BMSCs.The administration of SDF-1? in lung promoted the repair of seawater-induced lung injury by BMSCs.ConclusionBMSCs effectively treated seawater inhalation lung injury,and regulating SDF-1?/CXCR4 signal promoted the migration and colonization of BMSCs to the damaged lung tissue,thus promoting the repair of seawater inhalation lung injury.