Role Of Resistin-like Molecule α In Severe Acute Pancreatitis And Acute Pancreatitis Associated Lung Injury

Background: Acute pancreatitis(AP)is an acute inflammatory disease.With the change of the way of human life,morbidity is increasing in the recent years.Severe acute pancreatitis(SAP)could activate leukocyte cascade effect,lead to result in systemic inflammatory response syndrome(SIRS),and finally cause death.In the early phase of SAP,acute pancreatitis associated lung injury(APALI)is one of the most common and the most severe complications.With distinctive pulmonary distribution,Resistin-like molecule α(RELMα)has diverse regulatory functions in different inflammation,i.e.asthma,parasitic infection,chronic hypoxia,etc.But its role in SAP and APALI remains unclear.Methods: SAP and acute edematous pancreatitis(AEP)were respectively induced by retrograde infusion of 3.5% sodium taurocholatein and intraperitoneal injection of arginine in rats.Serum amylase and C-reactive protein(CRP),RELMα protein expression in lung tissue of rats was detected to determine the relationship between APALI and RELMα.For investigating the effect of RELMα on APALI,the rats were given an intravenous injection of RELMα overexpression adenovirus vector before SAP induction.Lung and pancreatic samples were harvested 16 h after induction.After detection of pulmonary RELMα protein levels,the severity of pancreatic and pulmonary injury was scored histologically,and serum and tissue levels of inflammatory mediators were measured.For verifying results of above experiment from another aspect,the rats were given an intravenous injection of targeted RELMα knockdown adenovirus vector before SAP induction,and performe above tests.TUNEL assay and immunofluorescence were used for estimating pulmonary apoptosis and endothelial barrier integrity in lung tissue of SAP rats with RELMα knockdown.Results: The pulmonary RELMα expression were remarkable increased in SAP rats and without increasing in AEP rats.The increasing was significantly associated with the lung injury index.RELMα overexpression aggravated the release of inflammatory cytokines including interleukin(IL)-1β,IL-6,IL-8,tumor necrosis factor-α,and serum C-reaction protein;the expression of inflammatory mediators phosphorylated(p)-AKT,p-P65,p-P38 mitogen activated protein kinase(p-P38 MAPK),p-extracellular regulated kinase(p-ERK),and intracellular adhesion molecule-1;and lung injury.RELMα knockdown had opposite effects.In addition,RELMα knockdown improved the expression of proliferative cellular nuclear antigen(PCNA),B-cell lymphoma-2(Bcl-2),apoptosis,zonal occluding-1 and Claudin-1 in lung tissue of SAP rats.Conclusions: RELMα is associated with lung injury severity in SAP,The increasing of pulmonary RELMα expression is related with lung injury exacerbation.RELMα can augment inflammatory activity by up-regulating inflammatory cytokine release.In the pathological process of APALI,the increasing of pulmonary RELMα could up-regulated inflammatory mediators and aggravated inflammation.Therefore,targeted knockdowning RELMα expression and blocking downstream signal molecules of RELMα could treat APALI,which provide a direction for APALI therapy in early stage.