Analysis Of The Risk Factors And Screening Of Peripheral Blood Biomarkers For Aortic Dissection With Ensuing Lung Injury

Part I Analysis of the risk factors for aortic dissection with ensuing lung injuryObjective:Acute lung injury is a frequent and serious complication in patients with aortic dissection, respiratory insufficiency caused by acute lung injury that increases the risk of perioperative.This study is intended to explore risk factors of aortic dissection with ensuing acute lung injury, in order to improve the effect of the treatment of patients with aortic dissection and reduce the incidence of related complications.Methods:From January2006to January2013.323patients with aortic dissection were retrospectively analyzed.The patients were divided into two groups, group A and group B, on the basis of presence or absence of actue lung injury. Clinical data were recorded to establish a database. The clinical data was analysed using univariate analysis.multivariate logistic regression analysis.correlation analysis and ROC analysis.Results:323patients were enrolled in the study, mean age was53.1±11.8years, Stanford A aortic dissection had198case (61.30%), Stanford B aortic dissection had125case(38.70%),111patients(34.37%)had actue lung injury after aortic dissection, the mean oxygenation index of323patients was335±81, the oxygenation index of group A was273±42, the oxygenation index of group B was363±46. Univariate analysis risk factors are as follows, Stanford A aortic dissection (91vs102, P<0.05), acute phase (93vs105,P<0.05),WBC (13.73±3.85vs8.12±1.83,P< 0.05),hs-CRP (16.65±3.27vs8.13±2.35,P<0.05),aortic dissection involving the superior mesenteric artery (40vs19, P<0.05). According to multiariable logistic regression analysis,the independent risk factors were hs-CRP and WBC.Correlation analysis indicate that oxygenation index had negative correlation with hs-CRP and WBC. The result according to ROC analysis were reliable.Conclusion:This study find that34.37%of patients with aortic dissection appear actue lung injury. The relevant risk factors are Stanford A aortic dissection, acute phase, WBC, hs-CRP and aortic dissection involving the superior mesenteric artery, the hs-CRP and WBC are independent risk factors. Part II Analysis of peripheral blood leukocyte by whole-genome expression profile chip in actue aortic dissectionObjective:We hope to achieve the whole understanding of molecular biological mechanism of peripheral blood leukocyte in the transcription level according to gene expression profile, in order to provides the basis for research actue aortic dissection with ensuing actue lung injury.Methods:Agilent expression profile chip was used to identify the changes of gene expression profile in peripheral leukocyte between high risk of aortic dissection patients and actue aortic dissection patients.The data from gene chip was analyzed using bioinformatics,the differentially expressed genes were analyzed by clustering analysis, GO analysis and Pathway analysis, meanwhile we explored the biological function of these genes after aortic dissection.Results:515differentially expressed genes changed more than2.0times, included238up-regulated genes and277down-regulated genes. The differentially expressed genes mainly involve inflammation, immune, cell adhesion, regulation of extracellular matrix and cytoskeleton, oxidative stress, metabolism, coagulation and fibrinolysis, signal transduction, apoptosis and other biological processes.Conclusion:The following pathology of gene expression profile in peripheral leukocyte after actue aortic dissection is a complex biological process.Gene chip is a fast, accurate, efficient method to screen the differentially expressed genes which play the important role to elucidate the pathophysiologic mechanic in actue aortic dissection and to reveal biomarks. PartⅢ Experiment research on screening of peripheral blood biomarkers involved in actue aortic dissection with ensuing lung injuryObjective:The study verifies the relationship between MMP-9, S100A12, TGF-β1and actue lung injury from gene to protein in order to find the biomarkers of actue aortic dissection with ensuing actue lung injury.Methods:Healthy control group(group A), high risk of aortic dissection group(group B), actue aortic dissection with ensuing actue lung injury absent group(group C) and actue aortic dissection with ensuing actue lung injury present group(group D) were the groups analysed in this research. Collecting blood samples, the fluorescent quantitative PCR and ELISA method were used respectively to detect MMP-9, S100A12, TGF-betal mRNA and protein level in peripheral blood. Correlation analysis with MMP-9and hs-CRP was performed.Results:The mRNA and protein level of MMP-9in group D was significantly elevated and have statistical significance compared with group A, group B and group C.the mRNA and protein level of S100A12and TGF-β1in group D increased significantly compared with group A and group B, but it wasn’t statistically significant compared with group C.Correlation analysis was positive correlation between MMP-9and hs-CRP (r=0.807, P＜0.01)。 Conclusion:MMP-9may play an important role on the pathogenesis of actue aortic dissection with ensuing actue lung injury, which may be used as the auxiliary diagnostic marker for actue aortic dissection with ensuing actue lung injury.