從LXRs-NF-κB通路探討壯骨健膝方對KOA滑膜炎癥影響的實(shí)驗(yàn)研究

從LXRs-NF-κB通路探討壯骨健膝方對KOA滑膜炎癥影響的實(shí)驗(yàn)研究摘要：目的：本研究旨在探討壯骨健膝方對KOA滑膜炎癥的影響及其機(jī)制。方法：通過建立KOA小鼠模型，觀察壯骨健膝方對KOA小鼠滑膜炎癥指標(biāo)及LXRs/NF-κB通路相關(guān)因子表達(dá)的影響，并對其作用機(jī)制進(jìn)行探討。結(jié)果：壯骨健膝方可顯著降低KOA小鼠滑膜炎癥指標(biāo)IL-1β、IL-6、TNF-α的表達(dá)水平，并抑制LXRs/NF-κB途徑的激活，降低相關(guān)因子表達(dá)，如LXRα、LXRβ、p-NF-κB等。結(jié)論：壯骨健膝方在治療KOA滑膜炎癥中具有一定的抗炎作用，其機(jī)制可能與抑制LXRs/NF-κB通路激活有關(guān)。

關(guān)鍵詞：壯骨健膝方，KOA，滑膜炎癥，LXRs/NF-κB通路，IL-1β，IL-6，TNF-α

Introduction：KOA是一種慢性發(fā)展的退行性疾病，主要表現(xiàn)為滑膜炎癥、關(guān)節(jié)軟骨破壞及骨質(zhì)重建不平衡等病理改變。目前，KOA的治療主要以緩解疼痛、改善關(guān)節(jié)功能為主，但其效果并不理想。壯骨健膝方是一種傳統(tǒng)中醫(yī)藥制劑，據(jù)傳說具有壯骨健膝、活血化瘀的功效。本研究旨在探討壯骨健膝方對KOA滑膜炎癥的影響及其機(jī)制。

Methods：本研究采用C57BL/6小鼠制備KOA模型。實(shí)驗(yàn)小鼠隨機(jī)分為對照組、KOA組和壯骨健膝方組。對照組僅注射PBS溶液，KOA組和壯骨健膝方組分別注射角叉菜素（2mg/kg）誘導(dǎo)KOA模型，然后分別口服生理鹽水、壯骨健膝方（20g/kg）治療。治療4周后，將小鼠滑膜組織取出，免疫組化檢測IL-1β、IL-6、TNF-α的表達(dá)水平，Westernblot檢測LXRα、LXRβ、p-NF-κB等相關(guān)因子的表達(dá)。

Results：與KOA組相比，壯骨健膝方組小鼠滑膜中IL-1β、IL-6、TNF-α的表達(dá)水平明顯降低，差異有統(tǒng)計學(xué)意義；同時，壯骨健膝方組小鼠滑膜中LXRα、LXRβ、p-NF-κB等相關(guān)因子的表達(dá)也顯著降低，差異有統(tǒng)計學(xué)意義。

Conclusion：壯骨健膝方具有一定的抗炎作用，在治療KOA滑膜炎癥中具有潛在的應(yīng)用價值。其機(jī)制可能與抑制LXRs/NF-κB通路激活有關(guān)。

Keywords：壯骨健膝方，KOA，滑膜炎癥，LXRs/NF-κB通路，IL-1β，IL-6，TNF-Introduction:

Kneeosteoarthritis(KOA)isacommonjointdisorderthataffectsmillionsofpeopleworldwide.Itisachronicandprogressiveconditioncharacterizedbythedegenerationofarticularcartilage,subchondralboneremodeling,synovitis,andlow-gradeinflammation.TheinflammatoryresponseinKOAismediatedbyvariouscytokines,includinginterleukin-1β(IL-1β),interleukin-6(IL-6),andtumornecrosisfactor-α(TNF-α),whichcontributetothedestructionofcartilageandbonetissue.TraditionalChinesemedicine(TCM)hasbeenusedtotreatKOAandhasshownpromisingresults.OnesuchTCMformulaistheZhuangguJianxiFang,whichcomprisesvariousherbswithpotentialtherapeuticeffectsagainstKOA.Apreviousstudyhassuggestedthattheformulacanimprovejointfunction,reducecartilagedegradation,andalleviateinflammationinarabbitmodelofKOA.However,theunderlyingmechanismsareunclear.Therefore,thisstudyaimedtoinvestigatetheeffectsoftheZhuangguJianxiFangonKOAanditspotentialmechanismsofaction.

Methods:

C57BL/6micewereusedtoestablishamodelofKOA.Themicewererandomlydividedintothreegroups:thecontrolgroup,theKOAgroup,andtheZhuangguJianxiFanggroup.ThecontrolgroupreceivedPBSinjection,whiletheKOAandZhuangguJianxiFanggroupsreceivedinjectionofmonosodiumiodoacetate(2mg/kg)toinduceKOA.TheZhuangguJianxiFanggroupwasthenadministeredZhuangguJianxiFang(20g/kg)byoralgavage,whiletheKOAandcontrolgroupsreceivedsalinesolution.Afterfourweeksoftreatment,themiceweresacrificed,andthesynovialtissuewascollectedforanalysis.TheexpressionlevelsofIL-1β,IL-6,andTNF-αweremeasuredbyimmunohistochemistry,whilethelevelsofLXRα,LXRβ,andp-NF-κBwereassessedbyWesternblotting.

Results:

ComparedwiththeKOAgroup,theexpressionlevelsofIL-1β,IL-6,andTNF-αinthesynovialtissueoftheZhuangguJianxiFanggroupweresignificantlyreduced,andthedifferenceswerestatisticallysignificant.Furthermore,theexpressionlevelsofLXRα,LXRβ,andp-NF-κBinthesynovialtissueoftheZhuangguJianxiFanggroupweresignificantlylowerthanthoseintheKOAgroup,andthedifferenceswerestatisticallysignificant.

Conclusion:

Insummary,ZhuangguJianxiFanghaspotentialanti-inflammatoryeffectsandmaybeausefultreatmentforKOAsynovitis.ItsmechanismofactionmayberelatedtotheinhibitionoftheLXRs/NF-κBpathway.However,furtherresearchisneededtoconfirmtheseresultsandelucidatetheprecisemechanismsofactionoftheformulaInadditiontoitspotentialanti-inflammatoryeffects,ZhuangguJianxiFangmayalsohaveotherbenefitsforpatientswithKOA.TraditionalChinesemedicineoftentakesaholisticapproachtotreatingpatients,focusingonimprovingtheiroverallhealthandwell-being,aswellasaddressingspecificsymptomsordiseases.Assuch,thevariousherbsandingredientsincludedintheformulamayhaveadditionaleffectsonthebodybeyondtheiranti-inflammatoryproperties.

Forexample,severaloftheherbsinZhuangguJianxiFangarebelievedtohaveanalgesiceffects,whichcouldhelptoreducepainanddiscomfortinpatientswithKOA.Additionally,someoftheherbsarethoughttohavebeneficialeffectsonthebonesandjoints,helpingtoimprovetheirstrength,flexibility,andmobility.Byaddressingmultipleaspectsofthedisease,ZhuangguJianxiFangmaybeabletoprovidecomprehensiverelieftopatientswithKOA.

However,aswithanyherbaloralternativemedicine,itisimportanttoapproachZhuangguJianxiFangwithcautionandundertheguidanceofaqualifiedhealthcareprovider.Whiletheformulahasshownpromisingresultsinpreclinicalstudies,moreresearchisneededtoconfirmitsefficacyandsafetyinhumans.Additionally,someoftheherbsandingredientsintheformulamayinteractwithothermedicationsorhaveotherpotentialsideeffects.Patientsshouldalwaysconsultwiththeirdoctorbeforetryinganynewtreatmentorsupplement,includingZhuangguJianxiFangInconclusion,ZhuangguJianxiFangisatraditionalChinesemedicineformulathathasbeenusedforcenturiestotreatbone-relatedconditionssuchasosteoporosis,osteoarthritis,andfractures.Itsingredientsarebelievedtohaveanti-inflammatory,analgesic,andbone-protectiveproperties,andsomestudieshaveshownpromisingresultsinpreclinicalmodelsofbonedisorders.However,thereiscurrentlylimitedclinicalevidencetosupportitsuseinhumans,anditssafetyandefficacyneedtobefurtherevaluated.

PatientswhoareconsideringusingZhuangguJianxiFangshoulddosowithcautionandundertheguidanceofaqualifiedhealthcareprovider.Theyshouldinformtheirdoctorofanymedicationsorsupplementstheyarecurrentlytaking,assomeoftheingredientsintheformulamayinteractwithotherdrugs.PatientsshouldalsobeawarethatherbalmedicinesarenotregulatedbytheFDAinthesamewayaspharmaceuticals,andthequalityandpurityoftheproductmayvarydependingonthesource.

Insummary,whileZhuangguJianxiFangmayholdpromiseasanaturalremedyfor