Plasma IL-17A And LncRNA MCM9 Could Predict The Occurrence Of ARDS

Background:Acute respiratory distress syndrome(ARDS)is a clinical syndrome characterized by refractory hypoxemia caused by intrapulmonary and/or extrapulmonary causes,which has attracted much attention due to high morbidity and mortality.While ?2-receptor agonists,statins,monoclonal antibodies and tumor necrosis factor fusion proteins are effective for ARDS,it remains a life-threatening complex disease.While the development of organ support technologies such as mechanical ventilation,extracorporeal membrane lung(ECMO),continuous renal replacement therapy(CRRT)did not effectively improve the mortality of ARDS.Numerous studies have shown that biomarkers can help us better understand ARDS.These biomarkers include genomics,metabolomics,inflammation-related markers,endothelial cell-related markers,etc.At present,most scholars believe that the essence of ARDS is excessive inflammatory response to damage alveolar epithelium,capillaries and pulmonary parenchyma,resulting in increased alveolar-capillary membrane permeability,resulting in pulmonary edema,alveolar hyaline membrane formation and refractory hypoxemia.Pro-inflammatory cytokines and anti-inflammatory cytokines in plasma and bronchoalveolar lavage fluid are closely related to the occurrence,severity and prognosis of ARDS.Inflammatory factors can be used as biomarkers of ARDS.But the role of inflammatory mediators in predicting whether high-risk patients develop into ARDS remains unclear.The causes of ARDS include sepsis,severe trauma,septic shock,aspiration,pneumonia,etc.Most patients with these risk factors do not develop ARDS.Much evidence suggests that some patients with high-risk factors may be more likely to develop ARDS,further studies have found that genetic factors play an important role in the development of ARDS.And LncRNA is a class of noncoding RNA with lengths greater than 200 nucleotides,which plays a broad regulatory role at epigenetic,transcriptional and posttranscriptional levels.Some studies have also shown that LncRNA is associated with ARDS,but further studies are still needed.So we researched for inflammatory response and LncRNA in order to find corresponding biomarkers to predict the occurrence or prognosis of ARDS.Objectives:To investigate the predictive effects of inflammation and LncRNA on ARDS.Methods:1.The soluble proteins(TNF-??IL-17 A and other 5 cytokines)in the samples were quantitatively detected by flow cytometry.The early warning model was established based on these cytokines and clinical data.The model was verified by ROC curve.2.Arraystar Human LncRNA Microarray V5.0 was used to detect difference in plasma between ARDS and high-risk groups,then we validated by real-time PCRResults1.APACHE-II score,LIPS score,endotracheal intubation rate,PCT and CRP in ARDS group were higher than high-risk group,while the oxygenation index,Glasgow score,plasma total protein and albumin were lower(p < 0.05).There was no difference in gender,age and other general conditions.2.The plasma levels of TNF-a,IL-17 A,IL-10,IL-6 and IL-33 in ARDS and high-risk groups were significantly higher than those in the control group,and the levels of IL-17 A in ARDS group were lower than those in the high-risk group(p < 0.05).3.Plasma IL-17 A was negatively correlated with LIPS(r =-0.343,p = 0.043)and positively correlated with oxygenation index(r = 0.429,p = 0.01).The results of Logistic regression analysis and ROC curve analysis showed that plasma IL-17 A could be an early warning indicator of ARDS progression in high-risk patients,while other inflammatory factors had no predictive effect.Inflammatory factors could not predict the clinical outcome of ARDS and high-risk patients.4.23427 LncRNA were detected in the microarray.Compared with high-risk group,5,108 genes were up-regulated,5,690 genes were down-regulated and 11,629 genes were not significantly expressed in the ARDS group.Among them,the expression of 372 LncRNA(including 115 up-regulated genes and 157 down-regulated genes)showed statistical differences(p < 0.05).5.Gene Ontology pathway analysis showed that these differentially expressed genes were closely related to the activation of MHC-2,DNA recombination,DNA specific binding,cytokine secretion,methylation and platelet formation.6.The plasma expression of LncRNA MCM9 in the ARDS group was significantly higher than high-risk group(p < 0.05),suggesting that LncRNA MCM9 may be related to the occurrence of ARDS and may be a biomarker of ARDS to warn the occurrence of ARDS.Conclusions1.Abnormal expression of plasma inflammatory factors were associated with the pathogenesis of ARDS.The levels of plasma IL-17 A may be a biomarker for the early warning of ARDS,but cannot predict the prognosis.2.Plasma LncRNA may be a biomarker of ARDS,and LncRNA MCM9 may be an early warning of ARDS.