Traumatic injury is associated with reduced deoxyribonuclease activity and dysregulation of the actin scavenging system

作     者：Jon Hazeldine Robert J.Dinsdale David N.Naumann Animesh Acharjee Jonathan R.B.Bishop Janet M.Lord Paul Harrison 

作者机构：Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamWest MidlandsB152TTUnited Kingdom National Institute for Health Research Surgical Reconstruction and Microbiology Research CentreHeritage BuildingQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Scar Free Foundation Birmingham Centre for Burns ResearchUniversity Hospital Birmingham Foundation TrustQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Academic Department of Military Surgery and TraumaRoyal Centre for Defence MedicineQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Institute of Cancer and Genomic SciencesCentre for Computational BiologyUniversity of BirminghamEdgbastonBirminghamWest MidlandsB152TTUnited Kingdom 

出 版 物：《Burns & Trauma》 (烧伤与创伤（英文）)

年 卷 期：2021年第9卷第1期

页      面：558-572页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 1011[医学-护理学（可授医学、理学学位）] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 0836[工学-生物工程] 10[医学] 

基　　金：funded by the National Institute for Health Research(NIHR)Surgical Reconstruction and Microbiology Research Centre and the Scar Free Foundation.JML is supported by the NIHR Birmingham Biomedical Research Centre and the Medical Research Council(MRC)Versus Arthritis Centre for Musculoskeletal Ageing Research.The funding bodies had no role in the design of the study the collection analysis or interpretation of the data or in the writing of the manuscript 

主　　题：Cell-free DNA Deoxyribonuclease Extracellular actin scavenging system Pre-hospital Trauma 

摘      要：Background:Traumatic injury is associated with increased concentrations of cell-free DNA(cfDNA)in the circulation,which contribute to post-injury *** endonuclease deoxyribonuclease 1(DNase-1)is responsible for removing 90%of circulating ***,DNase activity was reported to be significantly reduced following major non-traumatic brain injury(TBI),but the processes responsible were not ***,it is not known how quickly following injury DNase activity is reduced and whether this also occurs after ***:At 3 post-injury time points(≤1,4–12 and 48–72 hours),blood samples were obtained from 155 adult trauma patients that had sustained an isolated TBI(n=21),TBI with accompanying extracranial injury(TBI^(+))(n=53)or an extracranial injury only(ECI)(n=81).In addition to measuring cfDNA levels and the activity and expression of DNase,circulating concentrations of monomeric globular action(G-actin),an inhibitor of DNase-1,and the actin scavenging proteins gelsolin(GSN)and vitamin D binding protein(VDBP)were determined and values compared to a cohort of healthy ***:Significantly elevated concentrations of plasma cfDNA were seen in TBI,TBI^(+)and ECI patients at all study time points when compared to healthy *** levels were significantly higher at≤1 hour post-injury in ECI patients who subsequently developed multiple organ dysfunction syndrome when compared to those who did *** DNase-1 protein was significantly elevated in all patient groups at all sampling time *** contrast,DNase enzyme activity was significantly reduced,with this impaired function evident in TBI^(+)patients within minutes of *** concentrations of G-actin were elevated in all patient cohorts in the immediate aftermath of injury and this was accompanied by a significant reduction in the levels of GSN and ***:The post-traumatic increase in circulating cfDNA that occurs following extracranial trauma and TBI