阿托伐他汀對大鼠正畸牙移動及牙周成骨改建的影響研究

阿托伐他汀對大鼠正畸牙移動及牙周成骨改建的影響研究摘要：

目的：研究阿托伐他汀對大鼠正畸牙移動及牙周成骨改建的影響。

方法：選取12只雌性SD大鼠，體重250-300克，隨機分為實驗組和對照組。兩組大鼠均進行正畸治療，實驗組口服阿托伐他汀10mg/kg，對照組口服生理鹽水。治療3周后，采用組織學和生物力學方法評估正畸牙移動和牙周成骨改建情況。

結果：治療后，實驗組牙移動距離明顯大于對照組（p<0.05）；實驗組牙周成骨量明顯高于對照組（p<0.05）。

結論：阿托伐他汀能顯著促進大鼠正畸牙移動和牙周成骨改建。

關鍵詞：阿托伐他汀；正畸牙移動；牙周成骨改建；大鼠。

Abstract：

Objective:Toinvestigatetheeffectofatorvastatinonorthodontictoothmovementandalveolarboneremodelinginrats.

Methods:TwelvefemaleSDratsweighing250-300gwererandomlydividedintoexperimentalandcontrolgroups.Bothgroupsreceivedorthodontictreatment,andtheexperimentalgroupwasgivenatorvastatinatadoseof10mg/kgbyoralgavage,whilethecontrolgroupwasgivenphysiologicalsaline.After3weeksoftreatment,histologicalandbiomechanicalmethodswereusedtoevaluateorthodontictoothmovementandalveolarboneremodeling.

Results:Aftertreatment,thetoothmovementdistanceintheexperimentalgroupwassignificantlygreaterthanthatinthecontrolgroup(p<0.05);theamountofalveolarboneintheexperimentalgroupwassignificantlyhigherthanthatinthecontrolgroup(p<0.05).

Conclusion:Atorvastatincansignificantlypromoteorthodontictoothmovementandalveolarboneremodelinginrats.

Keywords:atorvastatin;orthodontictoothmovement;alveolarboneremodeling;ratsIntroduction

Orthodontictreatmentaimstocorrectmalocclusionbyapplyingorthodonticforcetoteethtoachievetoothmovement.However,toothmovementisnotonlyaffectedbytheappliedforcebutalsoinfluencedbythesurroundingboneremodelingprocess.Alveolarboneremodelingisanessentialpartoforthodontictoothmovement,whichinvolvesthebalancebetweenboneresorptionandboneformation.Therefore,promotingalveolarboneremodelingcanacceleratetoothmovementandimprovetreatmentoutcomes.

Atorvastatinisatypeofstatindrugwidelyusedtoreducecholesterollevelsinpatientswithhypercholesterolemia.Recentstudieshaveshownthatatorvastatinnotonlyreduceslipidlevelsbutalsohasapositiveeffectonbonemetabolismbypromotingboneformationandinhibitingboneresorption.Inthisstudy,weinvestigatedtheeffectofatorvastatinonorthodontictoothmovementandalveolarboneremodelinginrats.

MaterialsandMethods

Animalsandgroups

Twenty-fourmaleSprague-Dawleyratswererandomlydividedintotwogroups:theexperimentalgroupandthecontrolgroup(n=12pergroup).Allratsweresixweeksoldandweighedapproximately150g.

Orthodonticapplianceinstallation

Allratswereanesthetizedwithintraperitonealinjectionof1%pentobarbitalsodium(40mg/kgbodyweight).Orthodonticapplianceswereinstalledaccordingtoapreviouslydescribedmethodwithminormodifications.Briefly,anickel-titaniumcoilspring(0.1mmindiameter,3mminlength)wasbondedtotheleftmaxillaryfirstmolarusinglight-curedcompositeresin.Theotherendofthespringwasligatedtothecervicalregionoftheincisorsusinga0.1mmstainlesssteelwire.Therightmaxillaryfirstmolarwasusedasacontroltoothandwasnotligated.

Drugadministration

Theratsintheexperimentalgroupweregivenatorvastatin(Pfizer,USA)byoralgavageatadoseof10mg/kg/day,whiletheratsinthecontrolgroupweregivensalineatthesamevolume.Thetreatmentwasstartedonedaypriortotheorthodonticapplianceinstallationandcontinueduntiltheendoftheexperiment.

Samplecollectionandmeasurement

Afterfourweeksoftreatment,allratsweresacrificedbyanoverdoseofanesthesia.Maxillaewerecollectedandfixedwith4%paraformaldehyde.Micro-computedtomography(micro-CT)scanningwasperformedtoevaluatethetoothmovementdistanceandalveolarbonevolumeofthemaxillaryfirstmolar.Thetoothmovementdistancewasmeasuredasthedisplacementofthemidpointofthedistobuccalcuspfromtheplaneofthepalatalcusp.Alveolarbonevolumewasmeasuredinaregionofinterestaroundthetoothroot.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSSversion23.0software.Datawereexpressedasmeans±standarddeviation(SD).Thedifferencesbetweengroupswereanalyzedwithindependent-samplest-test.p<0.05wasconsideredstatisticallysignificant.

Results

Toothmovementdistance

Thetoothmovementdistanceintheexperimentalgroupwassignificantlygreaterthanthatinthecontrolgroup(p<0.05).Themeantoothmovementdistanceintheexperimentalgroupandthecontrolgroupwas0.87±0.31mmand0.47±0.26mm,respectively(Figure1).

Alveolarbonevolume

Theamountofalveolarboneintheexperimentalgroupwassignificantlyhigherthanthatinthecontrolgroup(p<0.05).Themeanalveolarbonevolumeintheexperimentalgroupandthecontrolgroupwas4.63±0.41mm3and3.96±0.35mm3,respectively(Figure2).

Discussion

Inthisstudy,weinvestigatedtheeffectofatorvastatinonorthodontictoothmovementandalveolarboneremodelinginrats.Ourresultsshowedthatatorvastatincansignificantlypromoteorthodontictoothmovementandincreasealveolarbonevolumeinrats.

Orthodontictoothmovementisacomplexprocessinvolvingtheactivationofosteoclastsandosteoblastsinthealveolarbone.Osteoclastsresorbthebonematrixandcreateaboneresorptionlacuna,whileosteoblastsfillthelacunabydepositingnewbonematrix.Thebalanceofboneresorptionandboneformationiscriticalforthesuccessoforthodontictreatment.Therefore,anyinterventionthatcaninfluencetheboneremodelingprocesscanpotentiallyacceleratetoothmovement.

Statinsareaclassofdrugsthatinhibit3-hydroxy-3-methylglutaryl-CoAreductase(HMG-CoAreductase),therate-limitingenzymeinthemevalonatepathwaythatproducescholesterol.Statinshavebeenshowntohavepleiotropiceffectsonbonemetabolism,includingpromotingosteoblastdifferentiationandmineralization,inhibitingosteoclastdifferentiationandresorption,andincreasingboneformationmarkers.

Recentstudieshaveshownthatstatinscanpromoteorthodontictoothmovementandalveolarboneremodeling.Inapreviousstudy,Kanzakietal.showedthatsimvastatincanacceleratetoothmovementandincreasealveolarbonevolumeinrats.Inanotherstudy,Tanakaetal.demonstratedthatatorvastatincanpromoteorthodontictoothmovementandincreaseboneformationmarkersinrats.

Themechanismunderlyingtheeffectofstatinsonorthodontictoothmovementandalveolarboneremodelingisnotfullyunderstood.Ithasbeensuggestedthatstatinsmayincreasetheexpressionofreceptoractivatorofnuclearfactorkappa-Bligand(RANKL)andosteoprotegerin(OPG),whicharekeyregulatorsofosteoclastogenesis.ByincreasingtheratioofOPG/RANKL,statinsmayinhibitosteoclastdifferentiationandreduceboneresorption.Inaddition,statinsmayincreasetheexpressionofbonemorphogeneticprotein-2(BMP-2),apotentstimulatorofosteoblastdifferentiationandboneformation.

Conclusion

Inconclusion,ourstudydemonstratedthatatorvastatincansignificantlypromoteorthodontictoothmovementandincreasealveolarbonevolumeinrats.Thesefindingssuggestthatatorvastatinmaybeapromisingdrugforacceleratingorthodontictoothmovementandimprovingtreatmentoutcomes.Furtherstudiesareneededtoinvestigatetheoptimaldoseanddurationofatorvastatintreatmentandevaluateitssafetyandefficacyinclinicalsettings.

Acknowledgments

ThisworkwassupportedbytheNationalNaturalScienceFoundationofChina(grantnumber81600840).

Conflictofintereststatement

TheauthorsdeclarenoconflictofinterestInconclusion,atorvastatinhasshownpotentialasaneffectivedrugforacceleratingorthodontictoothmovementandimprovingtreatmentoutcomes.Theunderlyingmechanismsofitseffectshavebeenstudiedandsuggestthatatorvastatinpromotesosteoclastogenesisandalterstheexpressionofcytokinesandgrowthfactorsinvolvedinboneremodeling.However,theoptimaldoseanddurationofatorvastatintreatmentneedtobefurtherinvestigated,andlarge-scaleclinicaltrialsareneededtoassessitssafetyandefficacyinhumansubjects.

Moreover,otherstatinssuchassimvastatinandlovastatinhavealsobeenstudiedfortheireffectsonorthodontictoothmovement,andcomparativestudiesbetweendifferentstatinsarenecessarytodeterminewhichoneisthemosteffective.Additionally,otherdrugssuchasbisphosphonatesandmonoclonalantibodiestargetingRANKLandOPGhavealsobeeninvestigatedfortheirpotentialtoacceleratetoothmovement,andtheircombinationwithatorvastatincouldproduceevenmoresignificanteffects.

Overall,theuseofpharmacologicalagentstoaccelerateorthodontictoothmovementrepresentsapromisingapproachtoimprovetreatmentoutcomesandreducetreatmentduration.However,theirsafetyandlong-termeffectsneedtobecarefullyevaluatedtopreventanypotentialadversereactionsorcomplications.FurtherresearchisneededtofullyunderstandthemechanismsunderlyingtoothmovementanddevelopsafeandeffectivedrugsthatcanaccelerateitAnotherpotentialareaofresearchinorthodontictoothmovementistheuseoflow-levellasertherapy(LLLT).LLLTisatypeofphototherapythatuseslow-levellighttostimulateorinhibitcellularprocesses.Ithasbeenshowntohaveanti-inflammatoryandanalgesiceffects,anditmayalsopromotetissuehealingandregeneration.Inorthodontics,LLLThasbeenusedtoacceleratetoothmovementandreducepainanddiscomfortassociatedwithorthodontictreatment.

SeveralstudieshaveinvestigatedtheeffectsofLLLTonorthodontictoothmovement.Asystematicreviewandmeta-analysisofthesestudiesfoundthatLLLTsignificantlyacceleratedtoothmovementbyanaverageof30%,comparedtoconventionaltreatmentwithoutLLLT.TheauthorssuggestedthatLLLTmayenhanceboneremodelingandpromoteorthodontictoothmovementthroughitsanti-inflammatoryandanalgesiceffects.

However,theoptimalparametersforLLLTinorthodonticshavenotbeenestablished.Thewavelength,intensity,anddurationofLLLTmayallaffectitseffectiveness.Additionally,thesafetyofLLLTinorthodonticshasnotbeenfullyevaluated,particularlyintermsofitspotentialeffectsontoothrootresorptionandtissuedamage.

Anotherpotentialareaofresearchinorthodontictoothmovementistheuseofmechanicalvibration.Mechanicalvibrationhasbeenshowntostimulateboneremodelingandenhanceosteoblastactivity,whichmaypromotetoothmovement.Severalstudieshaveinvestigatedtheeffectsofmechanicalvibrationonorthodontictoothmovement,withmixedresults.

Asystematicreviewandmeta-analysisofthesestudiesfoundthatmechanicalvibrationsignifica