雌激素對失血性休克小鼠血管低反應(yīng)性的作用與機制研究

雌激素對失血性休克小鼠血管低反應(yīng)性的作用與機制研究摘要：

目的：本研究旨在探究雌激素對失血性休克小鼠血管低反應(yīng)性的影響及其機制。

方法：將50只同齡健康雄性C57BL/6小鼠隨機分為失血性休克組和對照組。分別在T0、T1、T2、T3、T4、T5時點采集小鼠外周血檢測各項指標，并通過組織學(xué)檢測失血性休克時各臟器組織形態(tài)和損傷情況，同時觀察雌二醇和細胞外ATP對失血性休克小鼠主動脈平滑肌細胞的影響。

結(jié)果：失血性休克小鼠主動脈收縮反應(yīng)降低，且雌二醇能夠明顯提高主動脈受體器官射電圖輸出（Emax）值，同時抑制細胞外ATP的對主動脈平滑肌細胞的抑制作用。組織學(xué)檢測結(jié)果顯示，失血性休克小鼠肝臟、肺部、腎臟均存在不同程度的組織結(jié)構(gòu)和細胞浸潤破壞，而雌二醇處理組則顯示出部分保護作用。

結(jié)論：本研究證實，雌激素能夠顯著提高失血性休克小鼠血管的收縮反應(yīng)，同時展現(xiàn)出部分保護作用。

關(guān)鍵詞：雌激素，失血性休克，主動脈收縮反應(yīng)，細胞外ATP

Abstract：

Objectives:Thisstudyaimedtoinvestigatetheeffectofestrogenonvascularhypo-reactivityinhemorrhagicshockmiceanditsmechanism.

Methods:FiftyhealthymaleC57BL/6micewererandomlydividedintohemorrhagicshockgroupandcontrolgroup.PeripheralbloodsampleswerecollectedandvariousindicatorsweretestedatT0,T1,T2,T3,T4,T5timepoints.Thehistologyofvariousorgansandtissueinjuriesduringhemorrhagicshockwerealsodetected.Meanwhile,theeffectofestradiolandextracellularATPonthemainarterysmoothmusclecellsofhemorrhagicshockmicewasobserved.

Results:Thecontractionresponseofthemainarteryinhemorrhagicshockmicedecreased,andestradiolcouldsignificantlyincreasetheEmaxvalueofthemainarteryreceptororganelectrophysiologicaloutput,andinhibittheinhibitoryeffectofextracellularATPonmainarterysmoothmusclecells.Histologicalexaminationshowedthattherewerevariousdegreesoftissuestructureandcellinfiltrationdamageintheliver,lungs,andkidneysofhemorrhagicshockmice,whiletheestradioltreatmentgroupshowedpartialprotectiveeffects.

Conclusion:Thisstudyconfirmedthatestrogencouldsignificantlyimprovethecontractionresponseofbloodvesselsinhemorrhagicshockmiceandexhibitpartialprotectiveeffects.

Keywords:estrogen,hemorrhagicshock,mainarterycontractionresponse,extracellularATHemorrhagicshockisalife-threateningconditioncausedbyacutebloodloss,whichcanleadtomultipleorgandysfunctionandeventuallydeath.Previousstudieshavesuggestedthatthefemalesexhormoneestrogenmayplayaprotectiveroleinhemorrhagicshock,buttheunderlyingmechanismsarestillunclear.

Inthisstudy,weusedamousemodelofhemorrhagicshocktoinvestigatetheeffectsofestrogenonthemainarterycontractionresponseandextracellularATlevels.Ourresultsshowedthatestrogentreatmentsignificantlyimprovedthecontractionresponseofbloodvesselsinhemorrhagicshockmice.Specifically,themaximumcontractionforceandslopeoftheconcentration-responsecurveofthemainarterywereincreased,indicatingthatestrogenmayenhancethecontractilityofbloodvessels.

Moreover,wefoundthatestrogentreatmentalsoreducedthelevelsofextracellularAT,amarkeroftissuedamageandinflammation.Thissuggeststhatestrogenmayhaveanti-inflammatoryandtissue-protectiveeffectsinhemorrhagicshock.

Histologicalanalysisfurtherrevealedthatestrogentreatmentpartiallyprotectedtheliver,lungs,andkidneysfromtissuedamageandcellinfiltration.Althoughtherewerestillsomedegreeoftissueinjuryandinflammationintheestrogentreatmentgroup,theseveritywassignificantlyreducedcomparedtothecontrolgroup.

Takentogether,ourresultssuggestthatestrogenmayimprovethecontractionresponseofbloodvesselsandexerttissue-protectiveeffectsinhemorrhagicshock.Thesefindingsmayhaveimportantimplicationsforthedevelopmentofnoveltherapiesforthislife-threateningconditionInadditiontotheimmediateeffectsonbloodvesselcontractionandtissueprotection,estrogenmayhavelong-termbenefitsinthemanagementofhemorrhagicshock.Ithasbeendemonstratedthatestrogencanpromotewoundhealingandtissueregenerationinvariouscontexts,includingskin,bone,andneuraltissue(Santiago-O'Farrilletal.,2013;Kozaketal.,2014;Zhangetal.,2018).Giventhewidespreadtissuedamagethatoccursinhemorrhagicshock,theregenerativepropertiesofestrogenmaybeparticularlybeneficialforrestoringorganfunctionandreducingtheriskofcomplicationssuchasinfectionandorganfailure.

Furthermore,estrogenmayhaveimmunomodulatoryeffectsthatcouldplayaroleinthetreatmentofhemorrhagicshock.Forexample,estrogenhasbeenshowntosuppresstheproductionofpro-inflammatorycytokinessuchasTNF-alphaandIL-1beta,whileincreasingthelevelsofanti-inflammatorycytokinessuchasIL-10(Maggiolinietal.,2010;Haasetal.,2013).Inthecontextofhemorrhagicshock,thiscouldhelptoreducethesystemicinflammatoryresponseandpreventthedevelopmentofsecondaryorgandamage.

However,itshouldbenotedthattherearesomepotentialrisksassociatedwiththeuseofestrogeninhemorrhagicshock,particularlyinmalepatients.Estrogenhasbeenshowntoincreasetheriskofthromboembolicevents,suchasdeepveinthrombosisandpulmonaryembolism,whichcouldexacerbatethecardiovascularinstabilitythatoccursinhemorrhagicshock(Canonicoetal.,2007).Moreover,thereissomeevidencetosuggestthatestrogencanhavedeleteriouseffectsontheimmunesystemincertaincontexts,suchasautoimmunedisorders(Ghazizadehetal.,2016).Therefore,theappropriateuseofestrogeninhemorrhagicshockwillrequirecarefulconsiderationofthepotentialrisksandbenefits,aswellasindividualizedtreatmentplanningbasedonpatientcharacteristicsandmedicalhistory.

Inconclusion,hemorrhagicshockremainsasignificantclinicalchallengewithhighmorbidityandmortalityrates.Whilethecurrentstandardofcarefocusesonrestoringbloodvolumeandperfusion,thereisgrowinginterestinidentifyingadjunctivetherapiesthatcanimproveoutcomesandreducecomplications.Ourfindingssuggestthatestrogenmayhavetherapeuticpotentialinhemorrhagicshock,byimprovingbloodvesselcontractionandtissueprotection.Furtherresearchisneededtoelucidatethemechanismsofestrogen'seffectsandtooptimizeitsuseintheclinicalsettingOnepotentialmechanismbywhichestrogenmayimproveoutcomesinhemorrhagicshockisthroughitseffectsontheimmunesystem.Itiswell-establishedthatestrogencanmodulateimmuneresponses,includingsuppressinginflammatorycytokinesandpromotinganti-inflammatorypathways.Inthecontextofhemorrhagicshock,excessiveinflammationcancontributetotissuedamageandorgandysfunction,whileanti-inflammatorymechanismsmaypromotetissuerepairandrecovery.Thus,estrogen'santi-inflammatoryeffectsmayhelptomitigatetheharmfulconsequencesofshock.

Inadditiontoitseffectsontheimmunesystem,estrogenmayalsohavedirecteffectsontissuesthatareimportantformaintainingcardiovascularfunctioninshock.Forexample,estrogenhasbeenshowntoenhancetheproductionofnitricoxide(NO),apotentvasodilatorthatpromotesbloodflowandoxygendeliverytotissues.Inaddition,estrogencanupregulatetheexpressionofproteinsthatcontributetotheintegrityoftheendothelialbarrier,whichcanreducetheleakageoffluidandcellsfrombloodvesselsintosurroundingtissues.

Estrogenmayalsohavebeneficialeffectsoncardiacfunctioninhemorrhagicshock.Studieshaveshownthatestrogencanprotectagainstischemicinjurytotheheart,byreducingreactiveoxygenspecies(ROS)productionandpreservingmitochondrialfunction.Thisisespeciallyrelevantinthecontextofshock,wherereducedbloodflowandoxygendeliverytotissuescancauseoxidativestressandmitochondrialdysfunction.Byprotectingagainstthesedamagingmechanisms,estrogenmayhelptopreservecardiacfunctionandreducetheriskofcomplicationssuchasmyocardialinfarctionorarrhythmias.

Finally,itisworthnotingthatestrogen'seffectsmaybeinfluencedbyavarietyoffactors,includingage,menopausalstatus,andunderlyinghealthconditions.Forexample,somestudiessuggestthatpostmenopausalwomenhaveahigherriskofmortalityfromhemorrhagicshock,whichmayberelatedtothelossofestrogen'sprotectiveeffectsoncardiovascularandimmunefunction.Similarly,womenwithpre-existingcardiovasculardiseaseorothercomorbiditiesmaynotrespondtoestrogentherapyinthesamewayashealthyindividuals.Thus,carefulconsiderationofeachpatient'sindividualriskfactorsandmedicalhistorymaybeimportantindeterminingthepotentialbenefitsandrisksofestrogentherapyinhemorrhagicshock.

Inconclusion,whilefurtherresearchisneededtofullyelucidatethemechanismsofestroge