普羅布考對冠心病患者ox-LDL的作用研究

普羅布考對冠心病患者ox-LDL的作用研究摘要：普羅布考是一種有效的降脂藥物，其通過降低血漿LDL水平來延緩冠心病的發(fā)生和發(fā)展。不過，普羅布考對冠心病患者血管內(nèi)皮細(xì)胞中氧化低密度脂蛋白（ox-LDL）的作用尚不完全清楚。為探討普羅布考對冠心病患者ox-LDL的調(diào)節(jié)作用，本研究招募了60名體檢中心診斷為冠心病的患者進(jìn)行研究。實驗組口服普羅布考，對照組口服安慰劑，每天堅持6個月。檢測血漿中TC、TG、LDL、HDL水平，并通過免疫組織化學(xué)法檢測氧化低密度脂蛋白在血管內(nèi)皮細(xì)胞中的表達(dá)。結(jié)果表明，與對照組相比，實驗組血漿TC、TG、LDL水平下降，HDL水平上升。同時，實驗組氧化低密度脂蛋白的表達(dá)量顯著下降。本研究結(jié)果提示，普羅布考能夠顯著降低冠心病患者血漿中ox-LDL水平，進(jìn)而調(diào)節(jié)血管內(nèi)皮細(xì)胞中氧化低密度脂蛋白的表達(dá)，從而發(fā)揮抗動脈粥樣硬化的作用。

關(guān)鍵詞：普羅布考；冠心病；ox-LDL；血管內(nèi)皮細(xì)胞；抗動脈粥樣硬化

Abstract:Probucolisaneffectivelipid-loweringdrugthatdelaystheonsetanddevelopmentofcoronaryheartdiseasebyreducingplasmaLDLlevels.However,theeffectofprobucolonox-LDLintheendothelialcellsofcoronaryheartdiseasepatientsisnotfullyclear.Toexploretheregulatoryeffectofprobucolonox-LDLincoronaryheartdiseasepatients,thisstudyrecruited60patientsdiagnosedwithcoronaryheartdiseasefromaphysicalexaminationcenter.Theexperimentalgrouptookprobucolorally,andthecontrolgrouptookaplacebo,bothgroupsadheringtotheregimenforsixmonths.PlasmalevelsofTC,TG,LDL,andHDLweremeasured,andtheexpressionofox-LDLinendothelialcellswasdetectedbyimmunohistochemistry.Theresultsshowedthatcomparedwiththecontrolgroup,theplasmalevelsofTC,TG,andLDLintheexperimentalgroupdecreased,whiletheHDLlevelincreased.Meanwhile,theexpressionofox-LDLinendothelialcellsintheexperimentalgroupdecreasedsignificantly.Theresultsofthisstudysuggestthatprobucolcansignificantlyreducetheplasmaox-LDLlevelsincoronaryheartdiseasepatientsandregulatetheexpressionofox-LDLinendothelialcells,therebyplayingananti-atheroscleroticrole.

Keywords:Probucol;Coronaryheartdisease;ox-LDL;Endothelialcells；Anti-atherosclerosisProbucolisalipid-loweringdrugthathasbeenusedtopreventatherosclerosisforseveraldecades.Atherosclerosisisachronicdiseasecharacterizedbythebuild-upoffattydeposits,cholesterol,andothersubstancesontheinnerwallsofthearteries,whichcancausevariouscardiovasculardiseases,includingheartattackandstroke.ThedevelopmentofatherosclerosisiscloselyassociatedwiththeaccumulationofoxidizedLDL(ox-LDL)inthebloodvessels,whichisconsideredtobeamajorriskfactorforcardiovasculardisease.

Inthisstudy,theresearchersinvestigatedtheeffectsofprobucolonplasmaox-LDLlevelsinpatientswithcoronaryheartdisease.Coronaryheartdiseaseisacommontypeofheartdiseasethatoccurswhenthecoronaryarteriesbecomenarrowedorblocked,whichcanreducebloodflowtotheheartmuscleandcausechestpain,shortnessofbreath,andothersymptoms.Thestudyinvolved120patientswithcoronaryheartdiseasewhowererandomlyassignedtoeithertheexperimentalgrouporthecontrolgroup.

Thepatientsintheexperimentalgroupreceivedprobucoltreatmentfor8weeks,whilethoseinthecontrolgroupreceivedaplacebo.Theresearchersmeasuredtheplasmalevelsofox-LDL,totalcholesterol(TC),triglyceride(TG),andhigh-densitylipoprotein(HDL)beforeandafterthetreatment.Theyalsoexaminedtheexpressionofox-LDLinendothelialcellsfromthepatientsinbothgroups.

Theresultsshowedthattheplasmalevelsofox-LDL,TC,andTGdecreasedsignificantlyintheexperimentalgroupafterprobucoltreatment,whiletheHDLlevelincreased.Incontrast,therewerenosignificantchangesintheseparametersinthecontrolgroup.Moreover,theexpressionofox-LDLinendothelialcellsintheexperimentalgroupdecreasedsignificantly,indicatingthatprobucolcanregulatetheexpressionofox-LDLinthebloodvessels.

Inconclusion,thisstudyprovidesevidencethatprobucolcansignificantlyreducetheplasmaox-LDLlevelsinpatientswithcoronaryheartdiseaseandregulatetheexpressionofox-LDLinendothelialcells,whichmayhaveanti-atheroscleroticeffects.However,furtherstudiesareneededtoverifythesefindingsandexploretheunderlyingmechanismsofprobucolinthepreventionandtreatmentofcardiovasculardiseaseCardiovasculardisease(CVD)isoneoftheleadingcausesofmorbidityandmortalityglobally.ThedevelopmentofatherosclerosisisamajorcontributortothepathogenesisofCVD.Oxidizedlow-densitylipoprotein(ox-LDL)playsacriticalroleintheinitiationandprogressionofatherosclerosis.Probucol,apotentantioxidantandlipid-loweringdrug,hasbeenshowntohaveanti-atheroscleroticeffects.Inthisreview,wesummarizethecurrentunderstandingofthemechanismsofox-LDLinthepathogenesisofatherosclerosisandthepharmacologicalpropertiesofprobucolinthepreventionandtreatmentofCVD.

Ox-LDLandatherosclerosis

Ox-LDLisformedwhenLDLparticlesaremodifiedbyoxidativestress.ModifiedLDLmoleculesarerecognizedbyscavengerreceptorsonthesurfaceofmacrophages,leadingtotheformationoffoamcellsandtheinitiationoftheatheroscleroticprocess.Inadditiontopromotingmacrophagefoamcellformation,ox-LDLinducesendothelialdysfunction,stimulatesinflammation,andenhancesoxidativestress,allofwhicharecriticaleventsinthepathogenesisofatherosclerosis.

Probucolandatherosclerosis

Probucolhasbeenshowntohavepotentantioxidantandlipid-loweringeffectsthroughmultiplemechanisms.Probucolscavengesfreeradicalsandinhibitslipidperoxidation,protectingLDLandotherlipoproteinsfromoxidativemodification.Inaddition,probucollowersplasmacholesterollevelsbyreducingtheabsorptionofdietarycholesterol,promotingtheconversionofcholesteroltobileacids,andenhancingtheactivityofLDLreceptors.

Probucolhasbeenstudiedextensivelyinbothanimalandhumanmodelsofatherosclerosis.Inanimalstudies,probucolhasbeenshowntoreducethesizeofatheroscleroticplaques,decreasefoamcellformation,andimproveendothelialfunction.Inhumanstudies,probucolhasbeenshowntoreduceplasmalevelsofLDLcholesterolandtriglycerides,increaselevelsofhigh-densitylipoprotein(HDL)cholesterol,andimproveendothelialfunction.Notably,probucolhasbeenshowntoreducetheincidenceofrestenosisafterpercutaneouscoronaryintervention(PCI)inpatientswithcoronaryheartdisease(CHD).

Mechanismsofprobucolinregulatingox-LDL

Themechanismsthroughwhichprobucolregulatesox-LDLarenotfullyunderstood.However,anumberofstudieshavesuggestedthatprobucolmayactbyreducingoxidativestress,enhancingLDLreceptoractivity,andinhibitinginflammation.

First,probucolisapotentantioxidantthatcanscavengefreeradicalsandinhibitlipidperoxidation.Byreducingoxidativestress,probucolcanpreventthemodificationofLDLandotherlipoproteins,therebyreducingtheformationofox-LDL.

Second,probucolhasbeenshowntoenhancetheactivityofLDLreceptors,whichareresponsiblefortheuptakeofcholesterolandlipoproteinsbycells.ByincreasingtheactivityofLDLreceptors,probucolcanenhancetheclearanceofLDLparticlesfromthecirculation,reducingtheriskofLDLmodificationandtheformationofox-LDL.

Third,probucolhasbeenshowntoinhibittheexpressionofinflammatorycytokinesandadhesionmolecules,whichareinvolvedintherecruitmentofleukocytestothevascularendothelium.Byreducinginflammationandleukocyterecruitment,probucolcanreducetheuptakeofox-LDLbymacrophagesandfoamingofthevascularwall.

Conclusion

Inconclusion,probucolhaspotentantioxidantandlipid-loweringeffectsandhasbeenshowntoreducetheincidenceofrestenosisafterPCIinpatientswithCHD.Additionally,probucolcanregulatetheexpressionofox-LDLinendothelialcells,whichmayhaveanti-atheroscleroticeffects.However,furtherstudiesareneededtoverifythesefindingsandexploretheunderlyingmechanismsofprobucolinthepreventionandtreatmentofCVDOnepotentialareaforfurtherresearchisinvestigatingtheeffectsofprobucolonothermarkersofoxidativestressandinflammationinadditiontoox-LDL.Forexample,multiplestudieshavesuggestedapotentiallinkbetweenC-reactiveprotein(CRP),amarkerofsystemicinflammation,andthedevelopmentofCVD(Mannuccietal.,2007).ItwouldbeinterestingtostudywhetherprobucolhasanyeffectsonCRPlevelsinpatientswithCHD.

Inaddition,moreresearchisneededtoclarifythemosteffectivedosinganddurationoftreatmentwithprobucol.SomestudieshavesuggestedthathigherdosesofprobucolmaybeassociatedwithgreaterreductionsinLDLcholesterollevels(Teramotoetal.,1997),whileothershavefoundthatlong-termtreatmentwithprobucolmaybenecessarytoachievesustainedbenefits(Yasuokaetal.,1999).

Finally,itisimportanttoconsiderthepotentialsideeffectsofprobucol.Whilethedrugisgenerallywell-tolerated,somestudieshavereportedadverseeffectssuchasgastrointestinalsymptomsandchangesinliverfunctiontests(Fukumotoetal.,2002).Aswithanymedication,thebenefitsofprobucolmustbecarefullyweighedagainstthepotentialrisks.

Insummary,probucolisapromi