Estrogen Receptor Hormone Agonists Limit Trauma Hemorrhage Shock-Induced Gut and Lung Injury in Rats 英文参考文献.docVIP

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Estrogen Receptor Hormone Agonists Limit Trauma Hemorrhage Shock-Induced Gut and Lung Injury in Rats 英文参考文献.doc

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Estrogen Receptor Hormone Agonists Limit Trauma Hemorrhage Shock-Induced Gut and Lung Injury in Rats 英文参考文献

EstrogenReceptorHormoneAgonistsLimitTrauma HemorrhageShock-InducedGutandLungInjuryinRats DanielleDoucet,ChiragBadami,DavidPalange,R.PaulBonitz,QiLu,Da-ZhongXu,KolenkodeB. Kannan,IrianaColorado,RenaFeinman,EdwinA.Deitch* DepartmentofSurgery,UniversityofMedicineDentistryofNewJersey(UMDNJ)-NewJerseyMedicalSchool,Newark,NewJersey,UnitedStatesofAmerica Abstract Background:Acutelunginjury(ALI)andthedevelopmentofthemultipleorgandysfunctionsyndrome(MODS)isamajor causeofdeathintraumapatients.Earlierstudiesintraumahemorrhagicshock(T/HS)havedocumentedthatsplanchnic ischemia leadingtogutinflammation andlossofbarrier functionis aninitialtriggeringeventthatleads togut-induced ARDSandMODS.SincesexhormoneshavebeenshowntomodulatetheresponsetoT/HSandproestrous(PE)femalesare moreresistanttoT/HS-inducedgutanddistantorganinjury,thegoalofourstudywastodeterminethecontributionof estrogenreceptor(ER)aandERbinmodulatingtheprotectiveresponseoffemaleratstoT/HS-inducedgutandlunginjury. Methods/PrincipalFindings:TheincidenceofgutandlunginjurywasassessedinPEandovariectomized(OVX)femalerats subjectedtoT/HSortraumashamshock(T/SS)aswellasOVXratsthatwereadministeredestradiol(E2)oragonistsforERa or ERb immediately prior to resuscitation. Marked gut and lung injury was observed in OVX rats subjected to T/HS as comparedtoPEratsorE2-treatedOVXratssubjectedtoT/HS.BothERaandERbagonistswereequallyeffectiveinlimiting T/HS-inducedmorphologicvillousinjuryandbacterialtranslocation,whereastheERbagonistwasmoreeffectivethanthe ERaagonistinlimitingT/HS-inducedlunginjuryasdeterminedbyhistology,Evan’sbluelungpermeability,bronchoalevolar fluid/plasmaproteinratioandmyeloperoxidaselevels.Similarly,treatmentwitheitherE2ortheERbagonistattenuatedthe induction of the intestinal iNOS response in OVX rats subjected to T/HS whereas the ERa agonist was only partially protective. Conclusions/Significance:OurstudydemonstratesthatestrogenattenuatesT/HS-inducedgutandlunginjuryandthatits protectiveeffectsaremediatedbytheactiv