Influence Of Berberine On Lung Inflammation And SuPAR Expression Level In Acute Respiratory Distress Syndrome

Part Ⅰ Effects and Mechanism of Berberine on the Inflammatory Injury of Acute Respiratory Distress Syndrome MiceObjective:The aim is to study the effects and mechanism of Berberine on the inflammatory injury of acute respiratory distress syndrome(ARDS).Methods:ARDS mice model was established based on lipopolysaccharide(LPS),and gave berberine intervention at the same time.HE staining was used to observe lung damage degree,and then measured the ratio of lung wet/dry weight.ELISA was used to detect the expression levels of inflammatory markers.Real-time PCR was also applied to detect the mRNA levels of inflammatory markers.Western blot was used to detect the expression levels of NF-κB signaling pathway.Results:Compared with control group,there was different degree of lung damage in mice induced with lipopolysaccharide,it could be observed that a large number of micro thrombus,hyperemia and hemorrhage within microvessels,and a large number of inflammatory cells infiltration in pulmonary interstitial and alveolar space,interval between alveolar was also thickened.Ratio of lung wet/dry weight was significantly increased,the levels of TNF-a and IL-6 were significantly increased,while IL-10 was significantly reduced.In addition,lipopolysaccharide can activate NF-κB signaling pathway in lung tissue of mice,and phosphorylation levels of p65 subunit was significantly rose.However,berberine intervention could significantly inhibit inflammation and damage of lung tissue,and significantly inhibited NF-κB signaling pathway and phosphorylation level of p65 subunit in mice induced by LPS.Conclusions:Berberine intervention might inhibit abnormal activation of NF-κB signaling pathway in lung tissue,which could reduce the inflammation of lung tissue in mice induced by lipopolysaccharide,and then improve inflammatory injury in lung.Part Ⅱ Level and Clinical Significance of Soluble Urokinase Plasminogen Activator Receptor in Mice with Acute Respiratory Distress SyndromeObjective:The aim was to study the expression level of soluble urokinase plasminogen activator receptor(suPAR)in ARDS mice,and the correlations between suPAR and the severity of lung injury and lung inflammation,and then to lay the theoretical basis and experimental basis for searching potential biomarkers for diagnosis and prediction of ARDS.Methods:ARDS mice model was established based on lipopolysaccharide(LPS),and gave berberine intervention at the same time.ELISA was used to detect the expression levels of inflammatory markers including TNF-a,IL-6,IL-10 and suPAR,and then detect the association between suPAR and the severity of lung injury and lung inflammation.Results:Compared with the control group,the content of serum suPAR was significantly increased in ARDS mice,and after given berberine intervention,the expression level of suPAR was obviously inhibited in the serum of ARDS mice(P<0.05).Correlation analysis results showed that the content of suPAR was significantly positively related to lung injury score,lung wet/dry weight ratio,and levels of proinflammatory factor TNF-a and IL-6,but had significant negative correlation with the content of anti-inflammatory factor I-10(P<0.05).Conclusions:The content of serum suPAR was significantly increased in mice with acute respiratory distress syndrome.In addition,the rise in suPAR level might reflect the severity of the inflammatory response and lung tissue damage in mice with acute respiratory distress syndrome.Part III Correlation of plasma suPAR expression with disease risk and severity as well as prognosis of sepsis-induced acute respiratory distress syndromeObjective:The aim of this study was to investigate the association of plasma suPAR expression with disease risk and severity as well as prognosis of sepsis-induced acute respiratory distress syndrome(ARDS).Methods:162 ARDS patients were consecutively enrolled in this study and categorized into sepsis-induced ARDS group(N=104)or non-sepsis-induced ARDS group(N=58)according to the cause of ARDS.Disease severity was evaluated as mild,moderate and severe disease based on lowest PaO2/FiO2 ratio.Acute Physiology and Chronic Health Evaluation(APACHE)II as well as Sequential Organ Failure Assessment(SOFA)scores were calculated.Serum procalcitonin(PCT)was detected by electro chemiluminescence immunoassay,and plasma suPAR was determined by enzyme-linked immunosorbent assay.Results:Sepsis-induced ARDS presented with elevated plasma suPAR level(P<0.001),serum PCT level(P<0.001),APACHE Ⅱ score(P<0.001)and SOFA score(P<0.001)compared with patients with non-sepsis-induced ARDS.Plasma suPAR level was positively correlated with disease severity(P<0.001),PCT level(P<0.001),APACHE II score(P<0.001)and SOFA score(P<0.001).Among 104 sepsis-induced ARDS patients,73 cases survived(survival group)while other 31 cased dies(non-survival group).Plasma suPAR level was greatly increased in non-survival group compared to survival group(P<0.001).Furthermore,ROC curve analysis illustrated that suPAR level presented good diagnostic value in predicting mortality with AUC 0.81(95%CI:0.73-0.89).Conclusions:Plasma suPAR is increased in sepsis-induced ARDS patients,and it correlates with higher disease severity and unfavorable prognosis.