褪黑素在小鼠體內的濃度分布和晝夜節(jié)律及對荷胃癌小鼠TAMs的影響褪黑素在小鼠體內的濃度分布和晝夜節(jié)律及對荷胃癌小鼠TAMs的影響

摘要

褪黑素是一種由松果體分泌的激素，與晝夜節(jié)律調控密切相關。在小鼠體內，褪黑素的濃度分布和晝夜節(jié)律存在差異，同時對腫瘤微環(huán)境中的免疫細胞TAMs也有影響。本文通過測量小鼠體內褪黑素的濃度分布和晝夜節(jié)律，探討了褪黑素對荷胃癌小鼠TAMs的影響以及其可能的機制。結果顯示，褪黑素在小鼠體內呈現(xiàn)晝夜節(jié)律規(guī)律，分布在不同器官和組織中的濃度也存在差異。同時，通過使用荷胃癌小鼠模型，在褪黑素處理組和對照組中比較TAMs的數(shù)量和活性，發(fā)現(xiàn)褪黑素可以顯著減少腫瘤微環(huán)境中的TAMs的數(shù)量和活性，從而抑制腫瘤生長。進一步的機制研究表明，褪黑素可以通過下調亞硝酸合酶的表達抑制TAMs的活性。這些結果表明褪黑素可以作為一種潛在的治療腫瘤的藥物。

關鍵詞：褪黑素；小鼠；晝夜節(jié)律；TAMs；荷胃癌

Abstract

Melatoninisahormonesecretedbythepinealglandthatiscloselyrelatedtotheregulationofcircadianrhythms.Inmice,melatoninconcentrationdistributionandcircadianrhythmsvary,andtheyalsohaveanimpactontumor-associatedmacrophages(TAMs)inthetumormicroenvironment.Inthisarticle,wemeasuretheconcentrationdistributionandcircadianrhythmsofmelatonininmiceandinvestigatetheeffectsofmelatoninonTAMsingastriccancermiceanditspossiblemechanisms.Theresultsshowthatmelatonininmicepresentsacircadianrhythm,andtheconcentrationdistributionindifferentorgansandtissuesvaries.Furthermore,usingagastriccancermousemodel,wecomparethenumbersandactivitiesofTAMsinthemelatonintreatmentgroupandthecontrolgroup,andfoundthatmelatonincansignificantlyreducethenumberandactivityofTAMsinthetumormicroenvironment,thusinhibitingtumorgrowth.FurthermechanisticstudieshaveshownthatmelatonincansuppresstheactivityofTAMsbydownregulatingtheexpressionofnitricoxidesynthase.Theseresultssuggestthatmelatoninmaybeapotentialtreatmentforcancer.

Keywords:melatonin;mice;circadianrhythm;TAMs;gastriccancerThecircadianrhythmplaysanimportantroleinregulatingvariousphysiologicalprocesses,includingsleep-wakecycles,hormonesecretion,andimmuneresponses.Melatonin,ahormonesecretedbythepinealgland,isoneofthekeyregulatorsofthecircadianrhythm.Itiswell-knownforitssleep-promotingandantioxidanteffects,andhasalsobeenshowntohaveanti-cancerproperties.

Tumor-associatedmacrophages(TAMs)areimmunecellsthatarepresentinthetumormicroenvironment.Theyplayacrucialroleinpromotingtumorgrowthandmetastasisbyproducinginflammatorycytokinesandpromotingangiogenesis.Therefore,targetingTAMshasemergedasapromisingstrategyforcancertherapy.

Inarecentstudy,researchersinvestigatedtheeffectofmelatoninonTAMsinamousemodelofgastriccancer.TheyfoundthatmelatonintreatmentsignificantlyreducedthenumberandactivityofTAMsinthetumormicroenvironment,leadingtotheinhibitionoftumorgrowth.ThissuggeststhatmelatoninmaybeapotentialtherapeuticagentforcancerbytargetingTAMs.

FurthermechanisticstudiesrevealedthatmelatonincansuppresstheactivityofTAMsbydownregulatingtheexpressionofnitricoxidesynthase,anenzymethatisinvolvedinproducingnitricoxide,asignalingmoleculethatpromotesinflammationandtumorgrowth.

Thisstudyprovidesnewinsightsintotheanti-cancermechanismsofmelatoninandhighlightstheimportanceofthecircadianrhythmincancertherapy.FurtherresearchisneededtoexplorethepotentialclinicaluseofmelatoninincancertreatmentInadditiontoitsroleincancerpreventionandtreatment,melatoninhasalsobeenstudiedforitstherapeuticpotentialinvariousotherhealthconditions.Oneoftheseconditionsisneurodegenerativediseases,suchasAlzheimer'sdisease,Parkinson'sdisease,andmultiplesclerosis.

Studieshaveshownthatmelatoninmayhaveaprotectiveeffectonnervecellsandcanreducetheproductionofinflammatorymoleculesthatcontributetotheprogressionofneurodegenerativediseases.Melatoninhasalsobeenfoundtoimprovesleepqualityinpatientswiththeseconditions,whichcanleadtoimprovedcognitivefunctionandoverallqualityoflife.

Anotherpotentialapplicationofmelatoninisinthetreatmentofcardiovasculardisease.Melatoninhasbeenshowntohaveabeneficialeffectonbloodpressure,cholesterollevels,andoxidativestress,allofwhichareriskfactorsforcardiovasculardisease.Melatoninmayalsohaveaprotectiveeffectontheheartandbloodvessels,helpingtopreventthedevelopmentandprogressionofcardiovasculardisease.

Melatoninhasalsobeenstudiedforitspotentialroleinimprovingfertilityandreproductivehealth.Studieshavefoundthatmelatoninmayhelpregulatethemenstrualcycleandimproveovulationinwomenwithinfertility.Inmen,melatoninhasbeenfoundtoimprovespermqualityandmotility,whichcanincreasethechancesofsuccessfulfertilization.

Whilemelatoninhasbeenshowntohaveawiderangeofpotentialhealthbenefits,itisimportanttonotethatmoreresearchisneededtofullyunderstanditseffectsandpotentialclinicalapplications.Additionally,melatoninsupplementationshouldonlybeusedunderthesupervisionofahealthcareprofessional,ashighdosesorprolongedusemayhaveadverseeffectsInrecentyears,therehasbeengrowinginterestinthepotentialhealthbenefitsofcertainnutrientsandsupplementsforimprovingmalefertility.Inparticular,anumberofstudieshavesuggestedthattheaminoacidL-arginine,themineralzinc,andthevitaminsCandEmayallplayimportantrolesinimprovingspermqualityandmotility,aswellasoverallmalereproductivehealth.

OnestudypublishedintheJournalofSexualMedicineinvestigatedtheeffectsofL-arginineandzincsupplementationonsemenqualityinhealthy,fertilemen.ThestudyfoundthatbothL-arginineandzincsignificantlyincreasedspermcount,motility,andmorphology,suggestingthatthesenutrientsmaybebeneficialforpromotingmalefertilityandreproductivehealth.

Meanwhile,studieshavealsosuggestedthatvitaminCandEmayplayimportantrolesinprotectingspermcellsfromoxidativestressanddamage,whichcancontributetopoorspermqualityandreducedfertility.AreportinthejournalFertilityandSterilityfoundthatsupplementationwithvitaminsCandEimprovedspermmotilityandsurvivalininfertilemen,whileanotherstudyinthejournalAndrologiafoundthatvitaminCsupplementationimprovedspermparametersinmenwitholigoasthenoteratozoospermia(acommonconditioncharacterizedbylowspermcount,poormotility,andabnormalmorphology).

Inadditiontothesenutrients,certainherbalsupplementshavealsobeeninvestigatedfortheirpotentialeffectsonmalefertility.Forexample,theherbTribulusterrestrishaslongbeenusedinAyurvedicmedicineasanaturalaphrodisiacandfertilityenhancer.Studieshavesuggestedthatthisherbmayimprovespermcount,motility,andmorphology,aswellasincreasetestosteronelevelsinmen.Otherherbs,suchasmacarootandashwagandha,havealsobeenstudiedfortheirpotentialeffectsonmalefertilityandsexualhealth.

Itisimportanttonotethatwhilethesenutrientsandsupplementsholdpromiseforpromotingmalefertility,moreresearchisneededtofullyunderstandtheireffectsandpotentialclinica