吳茱萸次堿通過靶向CK2α抑制TGF-β1-Smad3和NF-κB信號通路對db-db糖尿病小鼠系膜細胞發(fā)揮保護作用

吳茱萸次堿通過靶向CK2α抑制TGF-β1-Smad3和NF-κB信號通路對db-db糖尿病小鼠系膜細胞發(fā)揮保護作用吳茱萸次堿通過靶向CK2α抑制TGF-β1/Smad3和NF-κB信號通路對db/db糖尿病小鼠系膜細胞發(fā)揮保護作用

摘要：

本研究旨在探究吳茱萸次堿對db/db糖尿病小鼠系膜細胞的保護作用及其相關(guān)機制。實驗采用Westernblotting和免疫熒光染色等方法檢測吳茱萸次堿對TGF-β1/Smad3和NF-κB信號通路的影響。研究結(jié)果表明，吳茱萸次堿可以抑制TGF-β1/Smad3和NF-κB信號通路的活化，降低系膜細胞的膠原合成和炎癥反應(yīng)，從而發(fā)揮保護作用。進一步研究發(fā)現(xiàn)，吳茱萸次堿的作用與CK2α的抑制有關(guān)，且這種抑制具有靶向性。綜上所述，吳茱萸次堿通過靶向CK2α抑制TGF-β1/Smad3和NF-κB信號通路對db/db糖尿病小鼠系膜細胞發(fā)揮保護作用。

關(guān)鍵詞：吳茱萸次堿，CK2α，TGF-β1/Smad3，NF-κB，系膜細胞，糖尿病

Abstract:

ThisstudyaimedtoinvestigatetheprotectiveeffectofWuZhuYuCiJianagainstmesangialcellsindb/dbdiabeticmiceanditsrelatedmechanisms.WesternblottingandimmunofluorescencestainingwereusedtodetecttheeffectofWuZhuYuCiJianontheTGF-β1/Smad3andNF-κBsignalingpathways.TheresultsshowedthatWuZhuYuCiJiancaninhibittheactivationoftheTGF-β1/Smad3andNF-κBsignalingpathways,reducecollagensynthesisandinflammationinmesangialcells,andthusexertaprotectiveeffect.FurtherstudieshavefoundthattheroleofWuZhuYuCiJianisrelatedtotheinhibitionofCK2α,andthisinhibitionistargeted.Inconclusion,WuZhuYuCiJianexertsaprotectiveeffectonmesangialcellsindb/dbdiabeticmicebytargetingCK2αtoinhibittheTGF-β1/Smad3andNF-κBsignalingpathways.

Keywords:WuZhuYuCiJian,CK2α,TGF-β1/Smad3,NF-κB,mesangialcells,diabeteDiabetesisachronicdiseaseaffectingmillionsofpeopleworldwide.Diabeticnephropathy,characterizedbyabnormalkidneyfunction,isacommoncomplicationofdiabetes.Mesangialcellsplayavitalroleinmaintainingtheglomerularstructureandfunction,andtheirabnormalproliferationandinflammationarekeyfactorsinthedevelopmentofdiabeticnephropathy.

ThetraditionalChinesemedicineWuZhuYuCiJianhasbeenusedtotreatdiabetesanditscomplicationsforcenturies.Recentstudieshaveshownthatithasaprotectiveeffectonmesangialcellsindiabeticmice.Themechanismbehindthiseffectisstillunclear.

CK2α,aproteinkinase,isinvolvedinvariouscellularprocesses,includingcellproliferation,inflammation,andapoptosis.RecentstudieshaveshownthatinhibitingCK2αcanreduceinflammationandcollagensynthesisinmesangialcells.ThisledresearcherstoinvestigatewhetherWuZhuYuCiJian'sprotectiveeffectonmesangialcellsislinkedtoCK2α.

TheresultsofthesestudieshaveshownthatWuZhuYuCiJianinhibitsCK2α,whichinturninhibitstheTGF-β1/Smad3andNF-κBsignalingpathways.Thesepathwaysareinvolvedininflammationandcollagensynthesisinmesangialcells.Byinhibitingthem,WuZhuYuCiJianreducesinflammationandcollagensynthesisinmesangialcells,preventingabnormalproliferationandimprovingkidneyfunctionindiabeticmice.

Inconclusion,WuZhuYuCiJianhasaprotectiveeffectonmesangialcellsindiabeticmicebyinhibitingCK2αandtheTGF-β1/Smad3andNF-κBsignalingpathways.ThesefindingsprovidenewinsightsintothemechanismofactionofthistraditionalChinesemedicineandmayleadtothedevelopmentofnewtreatmentsfordiabeticnephropathyDiabeticnephropathyisaseriouscomplicationofdiabetesmellitusthatcanleadtoend-stagerenaldisease.Thereiscurrentlynocurefordiabeticnephropathy,andcurrentlyavailabletreatmentsfocusonmanagingsymptomsandslowingdiseaseprogression.Therefore,thereisaneedfornewtreatmentsthatcantargettheunderlyingmechanismsofthedisease.

TraditionalChinesemedicinehasbeenusedtotreatavarietyofmedicalconditions,includingdiabetesanditscomplications.WuZhuYuCiJianisatraditionalChinesemedicineformulathathasbeenusedtotreatkidneyandliverdisorders.RecentstudieshaveshownthatthisformulamayhaveaprotectiveeffectonthekidneysindiabeticmicebyinhibitingCK2αandtheTGF-β1/Smad3andNF-κBsignalingpathways.

InhibitionofCK2αisanimportantmechanismofactionofWuZhuYuCiJian.CK2αisaproteinkinasethathasbeenimplicatedinthedevelopmentofdiabeticnephropathy.InhibitionofCK2αcanreduceinflammationandimprovekidneyfunctionindiabeticmicebyreducingtheabnormalproliferationofmesangialcells.

TheTGF-β1/Smad3signalingpathwayalsoplaysakeyroleinthedevelopmentofdiabeticnephropathy.TGF-β1isagrowthfactorthatisinvolvedintheregulationofcellgrowth,differentiation,andproliferation.Indiabeticnephropathy,TGF-β1promotesthedevelopmentoffibrosisinthekidneys,leadingtothelossofkidneyfunction.TheSmad3proteinisadownstreamtargetofTGF-β1andisinvolvedinthesignalingpathwaythatleadstofibrosis.InhibitionoftheTGF-β1/Smad3signalingpathwaycanreducefibrosisandimprovekidneyfunctionindiabeticmice.

TheNF-κBsignalingpathwayisanotherimportantmechanismofactionofWuZhuYuCiJian.NF-κBisatranscriptionfactorthatplaysaroleintheregulationofinflammationandcellsurvival.Indiabeticnephropathy,NF-κBisactivated,leadingtoincreasedinflammationandoxidativestressinthekidneys.InhibitionofNF-κBcanreduceinflammationandimprovekidneyfunctionindiabeticmice.

Overall,WuZhuYuCiJianhasaprotectiveeffectonmesangialcellsindiabeticmicebyinhibitingCK2αandtheTGF-β1/Smad3andNF-κBsignalingpathways.ThesefindingsprovidenewinsightsintothemechanismofactionofthistraditionalChinesemedicineandmayleadtothedevelopmentofnewtreatmentsfordiabeticnephropathy.FurtherstudiesareneededtoexplorethepotentialtherapeuticapplicationsofWuZhuYuCiJianinhumansInadditiontoitspotentialbenefitsfordiabeticnephropathy,WuZhuYuCiJianmayalsohaveothertherapeuticuses.StudieshavesuggestedthatitcouldimprovecognitivefunctionandmemoryinanimalmodelsofAlzheimer'sdisease,possiblybyreducingoxidativestressandinflammationinthebrain.Otherresearchhasshownthatitmighthaveantitumoreffectsbyinhibitingthegrowthandproliferationofcancercells.

Furthermore,WuZhuYuCiJianhasbeenusedintraditionalChinesemedicinetotreatavarietyofotherconditions,includingdigestivedisorders,menstrualirregularities,andskinconditionssuchaseczemaandurticaria.Whilemoreresearchisneededtofullyunderstanditsmechanismsofactionandpotentialapplications,thesefindingssuggestthatWuZhuYuCiJianmaybeapromisingtherapeuticagentforarangeofhealthissues.

Itisworthnoting,however,thatlikealltraditionalmedicines,WuZhuYuCiJianshouldbeusedwithcautionandunderthesupervisionofaqualifiedhealthcareprovider.Whileitisgenerallyconsideredsafeandwell-tolerated,someindividualsmayexperiencesideeffectssuchasnausea,diarrhea,orallergicreactions.Additionally,traditionalmedicinescaninteractwithothermedicationsorsupplements,soitisimportanttoinformyourhealthcareproviderifyouaretakinganyotherdrugsorhaveanyunderlyinghealthconditions.

Inconclusion,WuZhuYuCiJianisatraditionalChinesemedicinethatshowspromiseforthetreatmentofdiabeticnephropathyandmayhaveothertherapeuticapplicationsaswell.B