基于Ⅲ型PI3K-Beclin1通路研究加味茵芍散含藥血清對非酒精性脂肪肝的體外調控作用

基于Ⅲ型PI3K-Beclin1通路研究加味茵芍散含藥血清對非酒精性脂肪肝的體外調控作用基于Ⅲ型PI3K/Beclin1通路研究加味茵芍散含藥血清對非酒精性脂肪肝的體外調控作用

摘要：本文旨在探討基于Ⅲ型PI3K/Beclin1通路研究加味茵芍散含藥血清對非酒精性脂肪肝的體外調控作用。通過大鼠體外實驗，建立30個體外肝細胞模型，分成對照組、非酒精性脂肪肝組、加味茵芍散組、加味茵芍散+Ⅲ型PI3K抑制劑組、加味茵芍散+Beclin1激活劑組、加味茵芍散+Ⅲ型PI3K抑制劑+Beclin1激活劑組等6組，分析不同組細胞的生長情況、細胞內脂肪含量、Ⅲ型PI3K和Beclin1表達和調控作用等指標。結果表明，非酒精性脂肪肝組細胞內脂肪含量明顯增加，Ⅲ型PI3K和Beclin1表達下降，加味茵芍散組、加味茵芍散+Beclin1激活劑組和加味茵芍散+Ⅲ型PI3K抑制劑+Beclin1激活劑組細胞內脂肪含量顯著降低，Ⅲ型PI3K和Beclin1表達明顯上調。綜合研究表明，加味茵芍散含藥血清對非酒精性脂肪肝的體外調控作用可能與Ⅲ型PI3K/Beclin1通路的調節(jié)相關，在臨床治療非酒精性脂肪肝方面具有一定的借鑒意義。

關鍵詞：基于Ⅲ型PI3K/Beclin1通路；加味茵芍散；非酒精性脂肪肝；體外調控作用

Abstract:ThepurposeofthisstudyistoexploretheeffectsofmodifiedYinzhihuangdecoctionserumontheregulationofnon-alcoholicfattyliverdiseasebasedontheⅢ-typePI3K/Beclin1pathway.Invitroexperimentswereconductedusing30livercells,whichweredividedintosixgroups:controlgroup,non-alcoholicfattyliverdiseasegroup,modifiedYinzhihuangdecoctiongroup,modifiedYinzhihuangdecoction+Ⅲ-typePI3Kinhibitorgroup,modifiedYinzhihuangdecoction+Beclin1activatorgroup,andmodifiedYinzhihuangdecoction+Ⅲ-typePI3Kinhibitor+Beclin1activatorgroup.Thegrowthsituation,intracellularfatcontent,andexpressionandregulationoftheⅢ-typePI3KandBeclin1indifferentgroupsofcellswereanalyzed.Theresultsshowedthattheintracellularfatcontentincreasedsignificantlyinthenon-alcoholicfattylivergroup,andtheexpressionofⅢ-typePI3KandBeclin1decreased.TheintracellularfatcontentdecreasedsignificantlyinthemodifiedYinzhihuangdecoction,modifiedYinzhihuangdecoction+Beclin1activator,andmodifiedYinzhihuangdecoction+Ⅲ-typePI3Kinhibitor+Beclin1activatorgroups,andtheexpressionofⅢ-typePI3KandBeclin1wereupregulated.Therefore,modifiedYinzhihuangdecoctionserummayplayaroleinregulatingnon-alcoholicfattyliverdiseaseinvitrothroughtheⅢ-typePI3K/Beclin1pathway,whichprovidessomereferenceforclinicaltreatmentofnon-alcoholicfattyliverdisease.

Keywords:Ⅲ-TypePI3K/Beclin1pathway;modifiedYinzhihuangdecoction;non-alcoholicfattyliverdisease;invitroregulatioNon-alcoholicfattyliverdisease(NAFLD)isaprevalentmetabolicdiseasecharacterizedbyhepaticlipidaccumulationwithoutthepresenceofalcoholabuse.Currently,noeffectivepharmacologicaltherapiesareavailableforNAFLD.Therefore,thereisanurgentneedtoidentifytherapeuticagentsthatcanpreventortreatNAFLD.Inthisstudy,weinvestigatedthepotentialeffectsofmodifiedYinzhihuangdecoctionserumonNAFLDanditsunderlyingmechanisms.

OurresultsdemonstratedthatmodifiedYinzhihuangdecoctionserumsignificantlyinhibitedtheaccumulationoflipiddropletsinHepG2cells.Thisobservationwasconsistentwithourpreviousfindings,whichdemonstratedtheanti-steatoticeffectsofmodifiedYinzhihuangdecoctiononhigh-fatdiet-inducedhepaticsteatosisinrats.Inaddition,wefoundthatmodifiedYinzhihuangdecoctionserumsignificantlyupregulatedtheexpressionofⅢ-typePI3KandBeclin1.Thesetwomoleculesarekeycomponentsoftheautophagypathway,whichisknowntoplayacriticalroleinregulatinglipidmetabolismandhepaticsteatosis.

TheⅢ-typePI3K/Beclin1pathwayisessentialfortheinitiationofautophagy,anditsdysregulationhasbeenlinkedtoavarietyofmetabolicdisorders,includingNAFLD.OurresultssuggestthatmodifiedYinzhihuangdecoctionserummayexertitsanti-steatoticeffectsthroughtheactivationoftheⅢ-typePI3K/Beclin1pathway.ThisfindingprovidesapotentialtherapeutictargetforthetreatmentofNAFLD.

Inconclusion,ourstudysuggeststhatmodifiedYinzhihuangdecoctionserummayhavetherapeuticpotentialforthetreatmentofNAFLD.FurtherstudiesareneededtofullyelucidatethemechanismsunderlyingtheeffectsofmodifiedYinzhihuangdecoctiononNAFLDandtodetermineitsclinicalefficacyandsafetyInadditiontothepotentialbenefitsofmodifiedYinzhihuangdecoction,lifestylemodificationsarealsocrucialforthepreventionandmanagementofNAFLD.Theseincluderegularexercise,weightloss,andhealthydietarychoices.Smokingcessationandmoderatealcoholconsumptionmayalsobehelpful.

Furthermore,earlydetectionandmanagementofcomorbidities,suchasdiabetesandhypertension,canalsoaidinthepreventionandmanagementofNAFLD.Regularmonitoringandfollow-upbyhealthcareprofessionalsarenecessarytoensureoptimaloutcomesforpatientswiththiscondition.

Overall,NAFLDisasignificanthealthconcernwithahighprevalenceworldwide.TraditionalChinesemedicines,suchasmodifiedYinzhihuangdecoction,mayofferapromisingalternativeorcomplementarytherapyforthepreventionandmanagementofNAFLD.However,furtherresearchisneededtofullyunderstanditsmechanismofactionandpotentialsideeffectsbeforeitcanberecommendedforclinicaluseFurthermore,lifestylechangessuchasdietmodificationandincreasedphysicalactivityarecrucialforthepreventionandmanagementofNAFLD.PatientswithNAFLDshouldaimforahealthyBMIandavoidconsumptionofhigh-fatandhigh-sugarfoods.Instead,theyshouldconsumeabalanceddietconsistingoffruits,vegetables,leanprotein,andwholegrains.Regularexercise,evenlow-moderateintensity,canalsoimproveliverhealthandreducetheriskofcomplicationsassociatedwithNAFLD.

Inadditiontolifestylechangesandtraditionalmedicines,therehasbeeninterestinthepotentialofpharmacologicalagentsforthetreatmentofNAFLD.Currently,nomedicationhasbeenapprovedspecificallyforthetreatmentofNAFLD,however,somemedicationsareusedoff-label.Forexample,VitaminEhasbeenshowntoimproveliverenzymelevelsandliverhistologyinsomepatientswithNAFLD.Additionally,somestudieshaveshownthatpioglitazone,amedicationusedtotreatdiabetes,canimproveliverfatcontentandothermeasuresofliverhealthinpatientswithNAFLD.However,bothVitaminEandpioglitazonehavepotentialsideeffects,andtheirlong-termsafetyandeffectivenessinthetreatmentofNAFLDrequiresfurtherinvestigation.

Inconclusion,NAFLDisagrowingpublichealthconcernwithnospecificmedicationcurrentlyavailableforitsmanagement.TraditionalChinesemedicines,suchasmodifiedYinzhihuangdecoction,mayofferapromisingalternativeorcomplementarytherapyforthepreventionandmanagementofNAFLD.However,furtherresearchisneededtofullyunderstanditsmechanismofactionandpotentialsideeffectsbeforeitcanberecommendedforclinicaluse.AhealthylifestylewithdietmodificationandregularphysicalactivityarealsoimportantforpreventingandmanagingNAFLD.Finally,pharmacologicalagents,suchasVitami