麥冬皂苷D干預(yù)模擬急進(jìn)高原大鼠心肌損傷的藥理作用及分子機(jī)制

麥冬皂苷D干預(yù)模擬急進(jìn)高原大鼠心肌損傷的藥理作用及分子機(jī)制摘要：本研究旨在探討麥冬皂苷D(DPD)干預(yù)模擬急進(jìn)高原大鼠心肌損傷的藥理作用及分子機(jī)制。采用模擬海拔5,500米環(huán)境下急進(jìn)的方法，建立大鼠急進(jìn)高原模型，并隨機(jī)分為對(duì)照組、模型組、DPD低劑量組和DPD高劑量組。結(jié)果表明，DPD可顯著降低急進(jìn)高原大鼠的心重量指數(shù)及心肌損傷標(biāo)志物的水平；同時(shí)，DPD還可提高大鼠血清中血管緊張素Ⅱ(AngⅡ)、內(nèi)皮素-1(ET-1)、腫瘤壞死因子-α(TNF-α)和白介素-6(IL-6)的水平，以及降低一氧化氮(NO)的含量。進(jìn)一步實(shí)驗(yàn)數(shù)據(jù)表明，DPD可能通過激活磷脂酰肌醇3-激酶/Akt信號(hào)通路，并減弱心肌細(xì)胞凋亡和氧化應(yīng)激等方面的影響，以實(shí)現(xiàn)其對(duì)急進(jìn)高原大鼠心肌損傷的保護(hù)作用。本研究結(jié)果提示，DPD具有保護(hù)心肌、減輕高原心肺疾病等方面的潛力，有望成為高原醫(yī)學(xué)領(lǐng)域的新型藥物。

關(guān)鍵詞：麥冬皂苷D；急進(jìn)高原；心肌損傷；磷脂酰肌醇3-激酶/Akt信號(hào)通路；心肌細(xì)胞凋亡

Abstract:ThisstudyaimedtoinvestigatethepharmacologicaleffectsandmolecularmechanismsofDendrobiumloddigesiipolysaccharideD(DPD)interventioninsimulatedmyocardialinjuryinratswithrapidhigh-altitudeascent.Ratsweretreatedwithsimulatedrapidhigh-altitudeascentat5500m,andrandomlydividedintocontrolgroup,modelgroup,low-doseDPDgroupandhigh-doseDPDgroup.ResultsshowedthatDPDsignificantlyreducedtheheartweightindexandmyocardialinjurybiomarkerlevelsinratswithrapidhigh-altitudeascent,whileincreasingthelevelsofangiotensinII(AngII),endothelin-1(ET-1),tumornecrosisfactor-α(TNF-α)andinterleukin-6(IL-6),aswellasdecreasingnitricoxide(NO)levelsinratserum.FurtherexperimentaldataindicatedthatDPDmayexertitsprotectiveeffectonmyocardialinjuryinratsbyactivatingthephosphatidylinositol3-kinase(PI3K)/Aktsignalingpathway,andreducingtheeffectsofmyocardialcellapoptosisandoxidativestress.TheresultsofthisstudysuggestthatDPDhaspotentialinprotectingtheheart,andalleviatinghighaltitudeheartandlungdiseases,andmaybecomeanewmedicineinthefieldofhigh-altitudemedicine.

Keywords:DendrobiumloddigesiipolysaccharideD;Rapidhighaltitudeascent;Myocardialinjury;Phosphatidylinositol3-kinase(Akt)/signalingpathway;MyocardialcellapoptosisInrecentyears,thenumberofpeoplewhotraveltohighaltituderegionshasincreasedsignificantly.However,rapidascenttohighaltitudecanleadtoaltitudesickness,includinghighaltitudeheartandlungdiseases.Thesediseasescancauseseriousharmtohumanhealth,especiallytothosewhoarenotacclimatizedtohighaltitudeenvironments.Therefore,itisnecessarytofindeffectivewaystopreventandtreatthesediseases.

DPD,extractedfromtheDendrobiumloddigesii,hasbeenshowntohavevariousbiologicalactivities,suchasantioxidant,antitumor,andimmune-enhancingeffects.Inthisstudy,theresearchersfoundthatDPDcanprotecttheheartfromrapidhighaltitudeascent-inducedinjury.Inparticular,DPDcanreducethereleaseofcardiacenzymesandtheoccurrenceofmyocardialhistopathologicaldamageinratssubjectedtorapidhighaltitudeascent.

TheresearchersfurtherinvestigatedthemechanismsunderlyingtheprotectiveeffectsofDPDontheheart.TheyfoundthatDPDcanactivatethePI3K/Aktsignalingpathway.Thispathwayplaysacrucialroleincellsurvivalandgrowth,anditsactivationcanreducetheoccurrenceofmyocardialcellapoptosisinducedbyrapidhighaltitudeascent.Additionally,DPDcanreducetheproductionofreactiveoxygenspecies(ROS)andincreasetheactivityofantioxidantenzymes,thusreducingoxidativestressintheheart.

Inconclusion,thisstudyhighlightsthepotentialofDPDasanewmedicineinthefieldofhigh-altitudemedicine.TheprotectiveeffectsofDPDontheheartmayserveasapromisingstrategyforpreventingandtreatinghighaltitudeheartandlungdiseases.However,furtherstudiesareneededtofullyelucidatethemechanismsofDPD'sactionsandtoexploreitspotentialclinicalapplicationsAdditionally,itisworthnotingthathighaltitudeheartandlungdiseasesnotonlyaffectthoselivinginhighaltituderegions,butalsoindividualswhotraveltohighaltitudeareasforleisureorworkpurposes.Thesediseaseshaveasignificantimpactonthequalityoflifeandcanevenbefatalifleftuntreated.

Currently,themainapproachtopreventingandtreatinghighaltitudeheartandlungdiseasesistoacclimatizeslowlytothehigheraltitudeortousemedications,suchasacetazolamideordexamethasone,toalleviatesymptoms.However,thesetreatmentshavetheirlimitations,andthereisaneedformoreeffectiveandtargetedtherapies.

ThediscoveryofDPDanditsprotectiveeffectsontheheartprovidesanewavenueforthedevelopmentoftherapiesthatspecificallytargethighaltitudeheartandlungdiseases.DPD,withitsabilitytoincreasetheactivityofantioxidantenzymes,mayalsohavepotentialapplicationsinothercardiovasculardiseaseswhereoxidativestressplaysarole.

Insummary,thestudyonDPDanditsprotectiveeffectsontheheartprovidesvaluableinsightsintothedevelopmentofnewtherapiesforhighaltitudeheartandlungdiseases.ThepotentialofDPDasamedicineinhighaltitudemedicinewarrantsfurtherinvestigation,anditsclinicalapplicationsincardiovasculardiseasesbeyondhighaltitude-relatedconditionsarealsoworthexploringFurthermore,thestudyonDPDalsoshedslightontheimportanceofmanagingoxidativestressintheheart.Whileoxidativestressisanaturalprocessthatoccursasaresultofmetabolism,excessiveoxidativestresscandamagecellsandcontributetothedevelopmentofvariousdiseases,includingcardiovasculardiseases.Therefore,identifyingnaturalcompoundslikeDPDthatcanmitigateoxidativestresscanhavebroadimplicationsforthepreventionandtreatmentofcardiovasculardiseases.

Moreover,DPD'sabilitytoprotecttheheartfromhypoxia-induceddamageunderscorestheimportanceofoxygenbalanceincardiovascularhealth.Hypoxiaoccurswhenthereisadeficiencyofoxygeninthetissues,anditcanleadtocelldamageanddeath.Highaltitudeheartandlungdiseases,aswellasothercardiovasculardiseases,areoftenassociatedwithhypoxia.Therefore,developinginterventionsthatcanmaintainoxygenbalanceinthebody,suchasusingDPDorothernaturalcompounds,canbecrucialinpreventingandtreatingthesediseases.

Insummary,thestudyonDPDprovidesapromisingavenueforthedevelopmentofnewtherapiesforhighaltitudeheartandlungdiseases.Itsabilitytomitigateoxidativestressandprotecttheheartfromhypoxia-induceddamagecanhaveb