Modulation of Syndecan-1 Shedding after Hemorrhagic Shock and Resuscitation 英文参考文献.docVIP

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Modulation of Syndecan-1 Shedding after Hemorrhagic Shock and Resuscitation 英文参考文献.doc

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Modulation of Syndecan-1 Shedding after Hemorrhagic Shock and Resuscitation 英文参考文献

ModulationofSyndecan-1SheddingafterHemorrhagic ShockandResuscitation RickyJ.Haywood-Watson1,JohnB.Holcomb1,2,ErnestA.Gonzalez3,ZhanglongPeng1,ShibaniPati1,2, PyongWooPark4,WeiWeiWang5,AnaMariaZaske2,TylerMenge1,RosemaryA.Kozar1* 1Department of Surgery, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America, 2Center for Translational Injury and Research (CeTIR), The University of Texas Health Science Center at Houston, Houston, Texas, United States of America, 3Department of Surgery, University of Texas Southwestern Austin, Austin, Texas, United States of America, 4Division of Respiratory Diseases, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, UnitedStatesofAmerica,5CenterforClinicalandTranslationalSciences, TheUniversityofTexasHealthScienceCenteratHouston,Houston,Texas,UnitedStatesof America Abstract Theearlyuseoffreshfrozenplasmaasaresuscitative agentafterhemorrhagicshockhasbeenassociatedwithimproved survival, but the mechanism of protection is unknown. Hemorrhagic shock causes endothelial cell dysfunction and we hypothesized that fresh frozen plasma would restore endothelial integrity and reduce syndecan-1 shedding after hemorrhagic shock. Aprospective, observational studyinseverely injured patients inhemorrhagic shockdemonstrated significantly elevated levelsofsyndecan-1 (554693ng/ml)afterinjury,whichdecreased withresuscitation (187636ng/ ml) but was elevated compared to normal donors (2761ng/ml). Three pro-inflammatory cytokines, interferon-c, fractalkine, and interleukin-1b, negatively correlated while one anti-inflammatory cytokine, IL-10, positively correlated withshedsyndecan-1. Thesecytokines allplayanimportant roleinmaintaining endothelial integrity. Aninvitromodel of endothelial injury then specifically examined endothelial permeability after treatment with fresh frozen plasma orlactated Ringers. Shock or endothelial injury disrupted junctional integrity and increased perm