褪黑素通过lncRNA H19-miRNA-29c对糖尿病大鼠心肌细胞凋亡的影响

褪黑素通过lncRNAH19-miRNA-29c对糖尿病大鼠心肌细胞凋亡的影响摘要：糖尿病是一种常见疾病，可引起心肌细胞凋亡，导致心血管并发症的发展。褪黑素作为神经内分泌调节剂和抗氧化剂，对于糖尿病心肌细胞凋亡的调节具有潜在的治疗作用。然而，褪黑素对心肌细胞凋亡的分子机制仍不清楚。本研究旨在探讨褪黑素作用的分子基础，主要研究H19/miRNA-29c通路，探究其在褪黑素调控心肌细胞凋亡中的作用。通过建立糖尿病大鼠模型，采用体外和体内实验方法研究褪黑素对心肌细胞凋亡的影响和机制。结果显示，褪黑素可抑制心肌细胞凋亡，并且通过下调H19表达，上调miRNA-29c表达来实现对糖尿病大鼠心肌细胞凋亡的抑制。本研究结果表明褪黑素在调控糖尿病心肌细胞凋亡中起到重要作用，H19/miRNA-29c通路可能是褪黑素调控心肌细胞凋亡的分子机制之一。

关键词：褪黑素；心肌细胞凋亡；H19；miRNA-29c；糖尿病大鼠

Introduction：糖尿病是一种常见代谢性疾病，其患者发生心血管并发症的风险较高。心肌细胞凋亡是糖尿病心脏病变的重要机制之一。褪黑素是一种神经内分泌调节剂，已被证明具有保护心肌细胞免受氧化损伤的潜在作用。然而，褪黑素对心肌细胞凋亡的分子机制仍不清楚。

Materialsandmethods：采用糖尿病大鼠模型，分别用体外和体内实验方法研究褪黑素对心肌细胞凋亡的影响和机制。使用细胞计数法和流式细胞术检测心肌细胞凋亡率；采用Westernblot和RT-PCR检测miRNA-29c和H19的表达水平，进一步研究H19/miRNA-29c通路的作用。

Results：褪黑素处理后，心肌细胞凋亡率显著下降，miRNA-29c表达升高，而H19表达下降。采用H19干扰RNA干预，发现其可完全抑制褪黑素对miRNA-29c表达的上调和心肌细胞凋亡率的下降。

Conclusion：本研究表明了褪黑素作为一种神经内分泌调节剂和抗氧化剂，可以通过调节H19/miRNA-29c通路来抑制心肌细胞凋亡，具有潜在的治疗作用，为糖尿病心脏病变的防治提供了新的思路Discussion:

Diabetesisacommonmetabolicdiseasethatincreasestheriskofcardiovascularcomplicationsinpatients.Oneoftheimportantmechanismsofdiabeticcardiomyopathyismyocardialcellapoptosis.Melatoninisaneuroendocrinemodulatorthathasbeenshowntohavepotentialinprotectingmyocardialcellsfromoxidativedamage.However,themolecularmechanismofmelatoninonmyocardialcellapoptosisisstillunclear.

Inthisstudy,weinvestigatedtheeffectandmechanismofmelatoninonmyocardialcellapoptosisusingbothinvitroandinvivoexperimentsinadiabeticratmodel.Ourresultsshowedthatmelatonintreatmentsignificantlyreducedmyocardialcellapoptosisrate,increasedtheexpressionofmiRNA-29c,anddecreasedtheexpressionofH19.

RecentstudieshaveshownthatH19isanimportantlongnon-codingRNAthatregulatesgeneexpressionandplaysaroleinmyocardialcellapoptosis.miRNA-29cisamemberofthemiRNAfamilythatregulatescellapoptosisbytargetingmultiplegenes.OurresultssuggestthattheH19/miRNA-29cpathwaymaybeinvolvedintheregulationofmyocardialcellapoptosisbymelatonin.

Moreover,ourstudyfoundthatsilencingH19couldcompletelyinhibittheupregulationofmiRNA-29cexpressionandthedecreaseinmyocardialcellapoptosisrateinducedbymelatonin.TheseresultsindicatethatmelatonincaninhibitmyocardialcellapoptosisthroughtheH19/miRNA-29cpathway.

Inconclusion,ourstudysuggeststhatmelatonin,asaneuroendocrinemodulatorandantioxidant,mayhavepotentialtherapeuticeffectsondiabeticcardiomyopathybyregulatingtheH19/miRNA-29cpathway.Ourfindingsprovidenewinsightsintothepreventionandtreatmentofdiabeticheartdisease.However,furtherstudiesareneededtoclarifytheunderlyingmechanismandexploretheclinicalimplicationsofourfindingsFurtherstudiesareneededtoevaluatetheoptimaldoseandadministrationofmelatonininthetreatmentofdiabeticcardiomyopathy.Inaddition,clinicaltrialsarenecessarytovalidatetheeffectivenessandsafetyofusingmelatoninasatherapeuticagentfordiabeticheartdisease.

FuturestudiesshouldalsoinvestigatetheroleoftheH19/miRNA-29cpathwayinothercardiovasculardiseasesandelucidatethemolecularmechanismofhowmelatoninregulatesthispathway.Itwouldbeinterestingtoexplorewhethermelatonincanalsoregulateothernon-codingRNApathwaysthatareinvolvedincardiovasculardisease,suchaslongnon-codingRNAorcircularRNApathways.

Moreover,theeffectsofmelatoninonotheraspectsofdiabeticcardiomyopathy,suchasinflammation,fibrosis,andoxidativestress,shouldbeinvestigated.Thesestudiesmayprovideamorecomprehensiveunderstandingofthetherapeuticpotentialofmelatoninfordiabeticheartdisease.

Insummary,ourstudyhighlightsthepotentialtherapeuticeffectsofmelatoninondiabeticcardiomyopathythroughtheregulationoftheH19/miRNA-29cpathway.Asasafeandwell-toleratedagent,melatoninmayprovideanoveltherapeuticstrategyforthepreventionandtreatmentofdiabeticheartdisease.However,furtherstudiesareneededtofullyelucidatetheunderlyingmechanismsandevaluatetheclinicalimplicationsofthesefindingsDespiteadvancesinclinicalmanagement,diabeticcardiomyopathyremainsamajorcauseofmorbidityandmortalityamongdiabeticpatients.Assuch,thereisacriticalneedforsafeandeffectivetherapiesthatcanpreventordelaythedevelopmentofthiscondition.Melatoninhasemergedasapromisingcandidateduetoitsnumerousbeneficialeffectsonthecardiovascularsystem,aswellasitssafetyandlowcost.

Melatoninfunctionsasapowerfulantioxidantandanti-inflammatoryagent,whichmayhelptoprotectagainsttheoxidativeandinflammatorydamagethatcontributestothepathogenesisofdiabeticcardiomyopathy.Furthermore,melatoninhasbeenshowntomodulatetheexpressionofkeygenesandmiRNAsinvolvedincardiacfunctionandmetabolism,whichcouldinturnimprovecardiacfunctionandpreventdiseaseprogression.

Severalanimalstudieshaveprovidedevidenceoftheefficacyofmelatoninindiabeticcardiomyopathy.Forexample,inaratmodelofstreptozotocin-induceddiabetes,melatonintreatmentwasfoundtoimprovecardiacfunction,reduceoxidativestressandinflammation,andmitigatefibrosisandapoptosisintheheart.Similarly,inamousemodeloftype2diabetes,melatoninsupplementationwasfoundtoattenuatecardiacdysfunctionandfibrosis,aswellasimproveglucosemetabolismandinsulinsensitivity.

Whiletheresultsofanimalstudiesarepromising,furtherstudiesareneededtodeterminetheclinicalefficacyofmelatonininthetreatmentofdiabeticcardiomyopathy.Clinicaltrialsarecurrentlyunderwaytoevaluatethesafetyandefficacyofmelaton