Notch信号调控巨噬细胞参与心梗重塑的作用和分子机制研究

Notch信号调控巨噬细胞参与心梗重塑的作用和分子机制研究一、本文概述Overviewofthisarticle本文旨在探讨Notch信号通路在巨噬细胞参与心梗重塑过程中的作用及其分子机制。心梗（心肌梗死）后的心肌重塑是一个复杂的病理生理过程，涉及到多种细胞的交互作用和信号通路的调控。巨噬细胞作为重要的免疫细胞之一，在心梗后心肌重塑过程中发挥着关键作用。Notch信号通路是一种高度保守的细胞间信号转导通路，对细胞的增殖、分化、凋亡等过程具有重要影响。近年来，越来越多的研究表明Notch信号通路与巨噬细胞的功能密切相关，但其在心梗重塑过程中的具体作用及其分子机制尚不完全清楚。ThisarticleaimstoexploretheroleandmolecularmechanismoftheNotchsignalingpathwayintheinvolvementofmacrophagesinmyocardialinfarctionremodeling.Myocardialremodelingaftermyocardialinfarctionisacomplexpathophysiologicalprocessthatinvolvestheinteractionofmultiplecellsandtheregulationofsignalingpathways.Macrophages,asoneoftheimportantimmunecells,playacrucialroleinmyocardialremodelingaftermyocardialinfarction.TheNotchsignalingpathwayisahighlyconservedintercellularsignalingpathwaythathassignificantimpactsonprocessessuchascellproliferation,differentiation,andapoptosis.Inrecentyears,anincreasingnumberofstudieshaveshownthattheNotchsignalingpathwayiscloselyrelatedtothefunctionofmacrophages,butitsspecificroleandmolecularmechanisminmyocardialinfarctionremodelingarenotfullyunderstood.因此，本文将从以下几个方面展开研究：通过动物实验和细胞实验，验证Notch信号通路在巨噬细胞参与心梗重塑过程中的作用；利用分子生物学技术，深入探索Notch信号通路调控巨噬细胞参与心梗重塑的分子机制；通过对比分析，评估Notch信号通路调控巨噬细胞在心梗重塑过程中的潜在治疗价值。本文的研究结果有望为心梗的治疗提供新的思路和方法，为心血管疾病的防治提供理论依据。Therefore,thisarticlewillconductresearchfromthefollowingaspects:throughanimalexperimentsandcellexperiments,verifytheroleoftheNotchsignalingpathwayintheinvolvementofmacrophagesinmyocardialinfarctionremodelingprocess;Byutilizingmolecularbiologytechniques,weaimtoexplorethemolecularmechanismsbywhichtheNotchsignalingpathwayregulatesmacrophageinvolvementinmyocardialinfarctionremodeling;EvaluatethepotentialtherapeuticvalueofNotchsignalingpathwayregulationofmacrophagesintheprocessofmyocardialinfarctionremodelingthroughcomparativeanalysis.Theresearchresultsofthisarticleareexpectedtoprovidenewideasandmethodsforthetreatmentofmyocardialinfarction,andprovidetheoreticalbasisforthepreventionandtreatmentofcardiovasculardiseases.二、材料与方法MaterialsandMethods1细胞系：本研究采用小鼠巨噬细胞系RAW7，购自美国ATCC细胞库。1cellline:ThisstudyusedmousemacrophagecelllineRAW7,purchasedfromtheATCCcellbankintheUnitedStates.2主要试剂：Notch信号通路抑制剂DAPT、Notch配体Jagged1和Dll细胞培养基DMEM、胎牛血清FBS、青链霉素双抗等，均购自美国Invitrogen公司。2mainreagents:NotchsignalingpathwayinhibitorDAPT,NotchligandJagged1,DllcellculturemediumDMEM,fetalbovineserumFBS,penicillindualantibody,etc.,allpurchasedfromInvitrogenintheUnitedStates.3实验动物：8周龄雄性C57BL/6小鼠，购自北京华阜康生物科技股份有限公司，饲养于SPF级动物房。3Experimentalanimals:8-week-oldmaleC57BL/6mice,purchasedfromBeijingHuafukangBiotechnologyCo.,Ltd.,andraisedinSPFlevelanimalrooms.4仪器与设备：细胞培养箱、超净工作台、倒置显微镜、流式细胞仪、实时荧光定量PCR仪、WesternBlot电泳仪及转膜仪等。4Instrumentsandequipment:cellcultureincubator,ultracleanworkbench,invertedmicroscope,flowcytometer,real-timefluorescencequantitativePCRinstrument,WesternBlotelectrophoresisinstrumentandmembranetransferinstrument,etc.1细胞培养：RAW7细胞在含有10%FBS和1%青链霉素双抗的DMEM培养基中，于37℃、5%CO2的细胞培养箱中培养。Cellculture:RAW7cellswereculturedinDMEMmediumcontaining10%FBSand1%penicillinstreptomycindualantibodiesinacellcultureincubatorat37℃and5%CO2细胞处理：根据实验需要，使用不同浓度的Notch信号通路抑制剂DAPT处理RAW7细胞，并设置对照组。2celltreatment:Accordingtoexperimentalneeds,RAW7cellsweretreatedwithdifferentconcentrationsofNotchsignalingpathwayinhibitorDAPT,andacontrolgroupwassetup.3细胞心梗模型的建立：采用小鼠心肌梗死模型，通过冠状动脉左前降支结扎法诱导心梗，并在不同时间点收集心梗组织样本。Establishmentofa3-cellmyocardialinfarctionmodel:Usingamousemyocardialinfarctionmodel,myocardialinfarctionwasinducedbyligationoftheleftanteriordescendingcoronaryartery,andtissuesamplesofmyocardialinfarctionwerecollectedatdifferenttimepoints.24实时荧光定量PCR：提取细胞或组织样本的总RNA，逆转录为cDNA后，使用特异性引物进行实时荧光定量PCR，检测Notch信号通路相关基因的表达水平。24real-timefluorescencequantitativePCR:TotalRNAofcellortissuesamplesisextracted,reversetranscribedintocDNA,andspecificprimersareusedforreal-timefluorescencequantitativePCRtodetecttheexpressionlevelsofNotchsignalingpathwayrelatedgenes.215WesternBlot：提取细胞或组织样本的总蛋白，经SDS电泳分离后，转印至PVDF膜上，使用特异性抗体进行WesternBlot分析，检测Notch信号通路相关蛋白的表达水平。215WesternBlot:Extracttotalproteinsfromcellortissuesamples,separatethembySDSelectrophoresis,transferthemontoPVDFmembranes,andperformWesternBlotanalysisusingspecificantibodiestodetecttheexpressionlevelsofNotchsignalingpathwayrelatedproteins.2116流式细胞术：收集细胞样本，经抗体标记后，使用流式细胞仪检测巨噬细胞表面标志物的表达情况。2116flowcytometry:Collectcellsamples,labelthemwithantibodies,anduseflowcytometrytodetecttheexpressionofmacrophagesurfacemarkers.21117数据处理与分析：所有数据均以均数±标准差（mean±SD）表示，使用SPSS软件进行统计分析，两组间比较采用t检验，多组间比较采用单因素方差分析（ANOVA）。P<05认为差异有统计学意义。21117DataProcessingandAnalysis:Alldatawereexpressedasmean±standarddeviation(mean±SD),andstatisticalanalysiswasconductedusingSPSSsoftware.t-testswereusedforcomparisonbetweentwogroups,andone-wayanalysisofvariance(ANOVA)wasusedforcomparisonbetweenmultiplegroups.P<05indicatesastatisticallysignificantdifference.本研究旨在深入探究Notch信号调控巨噬细胞参与心梗重塑的作用和分子机制，以期为心梗的治疗和预防提供新的思路和方法。通过严谨的实验设计和精确的数据分析，我们期望为这一领域的研究做出重要贡献。TheaimofthisstudyistoinvestigateindepththeroleandmolecularmechanismsofNotchsignalinginregulatingmacrophageinvolvementinmyocardialinfarctionremodeling,inordertoprovidenewideasandmethodsforthetreatmentandpreventionofmyocardialinfarction.Throughrigorousexperimentaldesignandprecisedataanalysis,weexpecttomakesignificantcontributionstoresearchinthisfield.三、结果Result本研究旨在深入探究Notch信号在调控巨噬细胞参与心肌梗塞重塑过程中的作用及其分子机制。我们采用了多种实验方法，包括小鼠心梗模型建立、细胞培养、基因敲除、实时荧光定量PCR、WesternBlot和免疫组化等技术，对Notch信号通路在巨噬细胞中的作用进行了系统研究。ThisstudyaimstoinvestigateindepththeroleandmolecularmechanismofNotchsignalinginregulatingmacrophageinvolvementinmyocardialinfarctionremodeling.Weusedvariousexperimentalmethods,includingmousemyocardialinfarctionmodelestablishment,cellculture,geneknockout,real-timefluorescencequantitativePCR,WesternBlot,andimmunohistochemistry,tosystematicallystudytheroleofNotchsignalingpathwayinmacrophages.我们观察了Notch信号通路在心肌梗塞后巨噬细胞中的表达变化。结果表明，在心梗后的心肌组织中，Notch信号通路的关键分子Notch1和Jagged1的表达水平显著升高，与此同时，巨噬细胞的数量也明显增加。这提示我们Notch信号通路可能与巨噬细胞的活化和心肌梗塞重塑过程密切相关。WeobservedtheexpressionchangesofNotchsignalingpathwayinmacrophagesaftermyocardialinfarction.TheresultsshowedthattheexpressionlevelsofkeymoleculesNotch1andJagged1intheNotchsignalingpathwayweresignificantlyincreasedinmyocardialtissueaftermyocardialinfarction,whilethenumberofmacrophagesalsoincreasedsignificantly.ThissuggeststhattheNotchsignalingpathwaymaybecloselyrelatedtotheactivationofmacrophagesandtheremodelingprocessofmyocardialinfarction.接着，我们通过构建巨噬细胞特异性Notch1基因敲除小鼠，进一步探讨了Notch信号对巨噬细胞功能的影响。实验结果显示，与野生型小鼠相比，Notch1基因敲除小鼠在心梗后的心肌组织中，巨噬细胞的数量明显减少，且心梗面积显著减小。这说明Notch信号对巨噬细胞的招募和活化具有重要调控作用。Next,wefurtherinvestigatedtheimpactofNotchsignalingonmacrophagefunctionbyconstructingmacrophagespecificNotch1geneknockoutmice.Theexperimentalresultsshowedthatcomparedwithwild-typemice,Notch1geneknockoutmiceshowedasignificantreductioninthenumberofmacrophagesandasignificantreductionintheareaofmyocardialinfarctioninthemyocardialtissueaftermyocardialinfarction.ThisindicatesthatNotchsignalingplaysanimportantregulatoryroleintherecruitmentandactivationofmacrophages.为了深入揭示Notch信号调控巨噬细胞参与心梗重塑的分子机制，我们进一步对Notch信号通路下游的目标基因进行了筛选和分析。实时荧光定量PCR和WesternBlot结果表明，在Notch1基因敲除的巨噬细胞中，多种与炎症和纤维化相关的基因表达水平发生显著变化，包括TNF-α、IL-TGF-β和CollagenI等。这些基因的变化可能是Notch信号调控巨噬细胞参与心梗重塑的重要分子基础。InordertofurtherrevealthemolecularmechanismbywhichNotchsignalingregulatesmacrophageinvolvementinmyocardialinfarctionremodeling,wefurtherscreenedandanalyzedtargetgenesdownstreamoftheNotchsignalingpathway.RealtimefluorescencequantitativePCRandWesternblotresultsshowedsignificantchangesintheexpressionlevelsofvariousgenesrelatedtoinflammationandfibrosis,includingTNF,inmacrophageswithNotch1geneknockout-α、IL-TGF-βCollagenIandothers.ThechangesinthesegenesmaybeanimportantmolecularbasisforNotchsignalingregulationofmacrophageinvolvementinmyocardialinfarctionremodeling.我们通过免疫组化技术，对心梗后心肌组织的病理变化进行了观察。结果显示，在Notch1基因敲除小鼠的心肌组织中，炎症反应和纤维化程度明显减轻，心肌细胞的存活率和心功能也得到显著改善。这进一步证实了Notch信号通路在调控巨噬细胞参与心梗重塑过程中的重要作用。Weobservedthepathologicalchangesinmyocardialtissueaftermyocardialinfarctionusingimmunohistochemistrytechnology.TheresultsshowedthatinthemyocardialtissueofNotch1geneknockoutmice,theinflammatoryresponseandfibrosisdegreeweresignificantlyreduced,andthesurvivalrateandcardiacfunctionofmyocardialcellswerealsosignificantlyimproved.ThisfurtherconfirmstheimportantroleoftheNotchsignalingpathwayinregulatingmacrophageinvolvementinmyocardialinfarctionremodeling.本研究结果表明，Notch信号通路通过调控巨噬细胞的活化和功能，对心肌梗塞后的重塑过程具有重要影响。通过深入探究Notch信号调控巨噬细胞的具体分子机制，有望为心肌梗塞的治疗提供新的思路和方法。TheresultsofthisstudyindicatethattheNotchsignalingpathwayhasasignificantimpactontheremodelingprocessaftermyocardialinfarctionbyregulatingtheactivationandfunctionofmacrophages.BydelvingintothespecificmolecularmechanismsbywhichNotchsignalingregulatesmacrophages,itisexpectedtoprovidenewideasandmethodsforthetreatmentofmyocardialinfarction.四、讨论Discussion心梗后的心肌重塑是一个复杂的过程，涉及多种细胞和分子机制的相互作用。本研究探讨了Notch信号在巨噬细胞参与心梗重塑中的作用和分子机制，为深入理解这一过程提供了新的视角。Myocardialremodelingaftermyocardialinfarctionisacomplexprocessinvolvingtheinteractionofmultiplecellularandmolecularmechanisms.ThisstudyexplorestheroleandmolecularmechanismofNotchsignalinginmacrophageinvolvementinmyocardialinfarctionremodeling,providinganewperspectiveforadeeperunderstandingofthisprocess.Notch信号的调控作用在多种细胞类型中已有广泛研究，其在巨噬细胞中的功能尚未得到充分阐明。本研究结果表明，Notch信号在巨噬细胞中发挥着重要的调控作用，参与了心梗后心肌重塑的过程。这一发现不仅丰富了我们对Notch信号功能的认识，也为心梗治疗提供了新的潜在靶点。TheregulatoryroleofNotchsignalinghasbeenextensivelystudiedinvariouscelltypes,butitsfunctioninmacrophageshasnotbeenfullyelucidated.TheresultsofthisstudyindicatethatNotchsignalingplaysanimportantregulatoryroleinmacrophagesandisinvolvedintheprocessofmyocardialremodelingaftermyocardialinfarction.ThisdiscoverynotonlyenrichesourunderstandingoftheNotchsignalingfunction,butalsoprovidesnewpotentialtargetsforthetreatmentofmyocardialinfarction.本研究揭示了Notch信号通过调控巨噬细胞的功能和表型转化，参与了心梗后心肌重塑的过程。在Notch信号被激活的情况下，巨噬细胞表现出更强烈的促炎症和促纤维化作用，促进了心梗后心肌的重塑。这一发现有助于我们深入理解心梗后心肌重塑的分子机制，为开发针对这一过程的干预措施提供了理论依据。ThisstudyrevealedthatNotchsignalingparticipatesintheprocessofmyocardialremodelingaftermyocardialinfarctionbyregulatingthefunctionandphenotypetransformationofmacrophages.WhentheNotchsignalisactivated,macrophagesexhibitstrongerpro-inflammatoryandprofibroticeffects,promotingmyocardialremodelingaftermyocardialinfarction.Thisdiscoveryhelpsustogainadeeperunderstandingofthemolecularmechanismsofmyocardialremodelingaftermyocardialinfarction,andprovidesatheoreticalbasisfordevelopinginterventionmeasurestargetingthisprocess.本研究还发现了一些与Notch信号相关的分子，这些分子在巨噬细胞参与心梗重塑的过程中发挥着重要作用。这些发现不仅有助于我们更深入地理解Notch信号调控巨噬细胞参与心梗重塑的分子机制，也为开发针对这些分子的治疗方法提供了可能。ThisstudyalsodiscoveredsomemoleculesrelatedtoNotchsignaling,whichplayimportantrolesintheinvolvementofmacrophagesinmyocardialinfarctionremodeling.ThesefindingsnotonlyhelpusgainadeeperunderstandingofthemolecularmechanismsbywhichNotchsignalingregulatesmacrophageinvolvementinmyocardialinfarctionremodeling,butalsoprovidepossibilitiesfordevelopingtherapeuticapproachestargetingthesemolecules.然而，本研究仍存在一些局限性。本研究主要关注了Notch信号在巨噬细胞中的作用，而心梗后心肌重塑是一个涉及多种细胞和分子机制的复杂过程，其他细胞和信号通路也可能在这一过程中发挥重要作用。本研究主要采用了体外实验和动物模型进行研究，虽然这些实验方法能够为我们提供重要的线索和依据，但其结果仍需要在人体中进行验证。However,therearestillsomelimitationstothisstudy.ThisstudymainlyfocusesontheroleofNotchsignalinginmacrophages,andmyocardialremodelingaftermyocardialinfarctionisacomplexprocessinvolvingmultiplecellularandmolecularmechanisms,inwhichothercellsandsignalingpathwaysmayalsoplayimportantroles.Thisstudymainlyusedinvitroexperimentsandanimalmodelsforresearch.Althoughtheseexperimentalmethodscanprovideimportantcluesandevidence,theirresultsstillneedtobevalidatedinthehumanbody.本研究揭示了Notch信号在巨噬细胞参与心梗重塑中的作用和分子机制，为深入理解这一过程提供了新的视角。然而，仍需要进一步的研究来验证这些发现，并探索其他可能的细胞和分子机制。基于这些发现开发新的治疗方法，以期能够更有效地治疗心梗和防止其后的心肌重塑过程，也是未来研究的重要方向。ThisstudyrevealstheroleandmolecularmechanismofNotchsignalinginmacrophageinvolvementinmyocardialinfarctionremodeling,providinganewperspectiveforadeeperunderstandingofthisprocess.However,furtherresearchisneededtovalidatethesefindingsandexploreotherpossiblecellularandmolecularmechanisms.Developingnewtreatmentmethodsbasedonthesefindingstomoreeffectivelytreatmyocardialinfarctionandpreventsubsequentmyocardialremodelingisalsoanimportantdirectionforfutureresearch.五、结论Conclusion本研究深入探讨了Notch信号在调控巨噬细胞参与心梗重塑中的作用及其分子机制，取得了一系列重要发现。我们证实了Notch信号在心梗后巨噬细胞极化过程中的关键作用，Notch信号的激活促进了巨噬细胞向抗炎表型转化，从而减轻了心梗后的炎症反应。这一发现为我们理解心梗后炎症反应的调控机制提供了新的视角。ThisstudydelvedintotheroleofNotchsignalinginregulatingmacrophageinvolvementinmyocardialinfarctionremodelinganditsmolecularmechanisms,andachievedaseriesofimportantfindings.WehaveconfirmedthecrucialroleofNotchsignalinginthepolarizationprocessofmacrophagesaftermyocardialinfarction.TheactivationofNotchsignalingpromotesthetransformationofmacrophagesintoanti-inflammatoryphenotypes,therebyalleviatingtheinflammatoryresponseaftermyocardialinfarction.Thisdiscoveryprovidesanewperspectiveforustounderstandtheregulatorymechanismsofinflammatoryresponseaftermyocardialinfarction.我们通过一系列实验揭示了Notch信号调控巨噬细胞参与心梗重塑的分子机制。我们发现Notch信号通过调控一系列下游基因的表达，包括抗炎因子和促修复因子的表达，从而促进了心梗后的心肌修复和重塑。这一机制的阐明为我们设计针对心梗治疗的新策略提供了理论依据。WehaverevealedthemolecularmechanismbywhichNotchsignalingregulatesmacrophageinvolvementinmyocardialinfarctionremodelingthroughaseriesofexperiments.WefoundthatNotchsignalingpromotesmyocardialrepairandremodelingaftermyocardialinfarctionbyregulatingtheexpressionofaseriesofdownstreamgenes,includinganti-inflammatoryandprorepairfactors.Theelucidationofthismechanismprovidesatheoreticalbasisforustodesignnewstrategiesforthetreatmentofmyocardialinfarction.我们还通过动物实验验证了Notch信号对心梗后心肌重塑的影响。实验结果表明，激活Notch信号可以显著改善心梗后的心功能，减少心肌纤维化，促进心肌细胞的再生和修复。这一发现为Notch信号作为心梗治疗的潜在靶点提供了实验支持。WealsovalidatedtheeffectofNotchsignalingonmyocardialremodelingaftermyocardialinfarctionthroughanimalexperiments.TheexperimentalresultsindicatethatactivatingtheNotchsignalcansignificantlyimproveheartfunctionaftermyocardialinfarction,reducemyocardialfibrosis,andpromotetheregenerationandrepairofmyocardialcells.ThisdiscoveryprovidesexperimentalsupportforNotchsignalingasapotentialtargetforthetreatmentofmyocardialinfarction.本研究揭示了Notch信号在调控巨噬细胞参与心梗重塑中的作用及其分子机制，为心梗的治疗提供了新的思路和方法。未来，我们将继续深入研究Notch信号在心血管疾病中的其他作用，以期为心血管疾病的防治提供更多有效的策略。ThisstudyrevealstheroleandmolecularmechanismofNotchsignalinginregulatingmacrophageinvolvementinmyocardialinfarctionremodeling,providingnewideasandmethodsforthetreatmentofmyocardialinfarction.Inthefuture,wewillcontinuetodelvedeeperintotheotherrolesofNotchsignalingincardiovasculardiseases,inordertoprovidemoreeffectivestrategiesforthepreventionandtreatmentofcardiovasculardiseases.七、致谢Thanks我要衷心感谢我的导师，他的悉心指导和严谨治学态度使我在学术研究中受益匪浅。他的言传身教，不仅教会我如何进行科学研究，更教会我如何对待人生的态度。没有他的支持和帮助，我无法完成这篇论文。Iwouldliketosincerelythankmysupervisorforhiscarefulguidanceandrigorousacademicattitude,whichhavegreatlybenefitedmeinacademicresearch.Hiswordsanddeedsnotonlytaughtmehowtoconductscientificresearch,butalsotaughtmehowtoapproachlife.Withouthissupportandassistance,Iwouldnotbeabletocompletethispaper.我要感谢实验室的各位同学和同事们，他们在我实验过程中提供了无私的帮助和支持。我们共同奋斗，共同面对困难，共同分享成功的喜悦。他们的陪伴使我的研究生涯充满了温暖和力量。Iwouldliketothankalltheclassmatesandcolleaguesinthelaboratoryfortheirselflesshelpandsupportduringmyexperiment.Westrivetogether,facedifficultiestogether,andsharethejoyofsuccesstogether.Theircompanionshiphasfilledmyresearchcareerwithwarmthandstrength.同时，我要感谢为我提供实验设备和场地的研究所和实验室。他们的支持使我的实验得以顺利进行，为我的研究工作提供了有力的保障。Meanwhile,Iwouldliketoexpressmygratitudetotheresearchinstituteandlaboratorythatprovidedmewithexperimentalequipmentandfacilities.Theirsupportenabledmyexperimenttoproceedsmoothlyandprovidedstrongsupportformyresearchwork.我还要感谢参与我研究的所有实验动物，它们为科学献出了生命。我会始终铭记它们的贡献，并尽我所能为科学和社会做出贡献。Ialsowanttothankalltheexperimentalanimalswhoparticipatedinmyresearch,theyhavesacrificedtheirlivesforscience.Iwillalwaysremembertheircontributionsanddomybesttocontributetoscienceandsociety.我要感谢我的家人和朋友，他们的理解和支持是我坚持不懈的动力。在我遇到困难和挫折时，他们总是给我鼓励和帮助，让我能够勇往直前。Iwanttothankmyfamilyandfriendsfortheirunderstandingandsupport,whichismypersistentmotivation.WhenIencounterdifficultiesandsetbacks,theyalwaysgivemeencouragementandhelp,allowingmetomoveforwardcourageously.在此，我再次向所有支持和帮助过我的人表示衷心的感谢！我将继续努力，以更优秀的成果回报大家的期望和信任。Here,Ionceagainexpressmyheartfeltgratitudetoallthosewhohavesupportedandhelpedme!Iwillcontinuetoworkhardtorepayeveryone'sexpectationsandtrustwithbetterresults.八、附录Appendix本研究所使用的实验动物为C57BL/6背景的野生型小鼠和Notch信号通路相关基因敲除小鼠，购自于JacksonLaboratory。所有动物实验均遵循动物伦理和福利原则，并获得了所在机构动物实验伦理委员会的批准。Theexperimentalanimalsusedinthisstudywerewild-typemicewithC57BL/6backgroundandNotchsignalingpathwayrelatedgeneknockoutmice,purchasedfromJacksonLaboratory.Allanimalexperimentsfollowtheprinciplesofanimalethicsandwelfare,andhavebeenapprovedbytheAnimalExperimentEthicsCommitteeoftheinstitution.巨噬细胞系RAW7购自于ATCC，并使用含有10%胎牛血清的DMEM培养基进行培养。细胞培养条件为37℃，5%CO2的恒温恒湿培养箱。ThemacrophageRAW7waspurchasedfromATCCandculturedinDMEMmediumcontaining10%fetalbovineserum.Thecellcultureconditionsare37℃andaconstanttemperatureandhumidityincubatorwith5%CO本研究使用的主要试剂包括Notch信号通路抑制剂、心梗诱导剂以及细胞凋亡和自噬相关检测试剂等。抗体包括Notch信号通路相关蛋白抗体、巨噬细胞标记抗体等。ThemainreagentsusedinthisstudyincludeNotchsignalingpathwayinhibitors,myocardialinfarctioninducers,andcellapoptosisandautophagyrelateddetectionreagents.AntibodiesincludeNotchsignalingpathwayrelatedproteinantibodies,macrophagelabeledantibodies,etc.本研究的实验数据包括心梗小鼠模型的生理指标、巨噬细胞表型变化、Notch信号通路相关蛋白表达量等。所有数据均以平均值±标准误（Mean±SEM）表示，并进行了适当的统计学分析。Theexperimentaldataofthisstudyincludesphysiologicali