理氣補(bǔ)血湯調(diào)控TGF-β1-Smad通路延緩失神經(jīng)骨骼肌萎縮的機(jī)制研究

理氣補(bǔ)血湯調(diào)控TGF-β1-Smad通路延緩失神經(jīng)骨骼肌萎縮的機(jī)制研究摘要：目的：探討理氣補(bǔ)血湯對于失神經(jīng)骨骼肌萎縮的機(jī)制研究，特別是在調(diào)控TGF-β1/Smad通路方面的作用。方法：選取2組老年小鼠，將其中1組投予理氣補(bǔ)血湯治療，另1組為對照組。實(shí)驗(yàn)分別在治療后及4周后進(jìn)行取材，檢測肌肉的質(zhì)量、力量以及相關(guān)生化指標(biāo)，同時利用免疫組化、Westernblot等方法檢測TGF-β1/Smad通路的變化。結(jié)果：在治療后，治療組小鼠肌肉的質(zhì)量及力量均有所增加，且TGF-β1/Smad通路的活性均相應(yīng)下降；而對照組小鼠的情況則較為穩(wěn)定。在治療后4周，治療組小鼠的肌肉質(zhì)量及力量仍保持在高水平，而對照組則有所下降。結(jié)論：理氣補(bǔ)血湯可通過調(diào)控TGF-β1/Smad通路的活性，達(dá)到延緩失神經(jīng)骨骼肌萎縮的作用。

關(guān)鍵詞：理氣補(bǔ)血湯，TGF-β1/Smad通路，肌肉萎縮，老年小鼠

Introduction

肌肉萎縮是一種常見的老年疾病，尤其是與失神經(jīng)有關(guān)的肌肉萎縮。肌肉萎縮不僅影響了老年人的身體功能，還對成年人的身體健康產(chǎn)生了嚴(yán)重的影響。盡管對于失神經(jīng)骨骼肌萎縮的研究已經(jīng)取得了一些成果，但目前缺少有效的治療手段。因此，研究一種有效治療失神經(jīng)骨骼肌萎縮的方法就顯得尤為必要。

理氣補(bǔ)血湯是一種中草藥復(fù)方，被廣泛應(yīng)用于治療各種疾病。理氣補(bǔ)血湯可滋養(yǎng)氣血，具有活血化瘀的作用，因此可以調(diào)節(jié)人體內(nèi)的氣血平衡。在老年人中，氣血的平衡是非常重要的，因?yàn)樯眢w過度消耗氣血，導(dǎo)致肌肉萎縮和其他健康問題。因此，本研究旨在探討理氣補(bǔ)血湯對于失神經(jīng)骨骼肌萎縮的作用及其可能的機(jī)制。

MaterialsandMethods

實(shí)驗(yàn)對象：選擇年齡為18-24個月的老年小鼠作為實(shí)驗(yàn)對象，根據(jù)體質(zhì)分為2組，每組10只。其中1組為治療組，另1組為對照組。

治療方案：將治療組小鼠投予理氣補(bǔ)血湯，每天2次，每次5ml。對照組則不進(jìn)行治療。

實(shí)驗(yàn)時間：實(shí)驗(yàn)分別在治療后及4周后進(jìn)行取材。

檢測指標(biāo)：采用生物力學(xué)測量儀檢測小鼠運(yùn)動能力；采用肌肉切片法觀察肌肉組織形態(tài)學(xué)變化；采用ELISA法檢測肌肉中TGF-β1水平；采用Westernblot檢測Smad及p-Smad的變化；采用免疫組化法檢測肌肉中相關(guān)細(xì)胞因子及蛋白質(zhì)的表達(dá)情況。

Results

1、理氣補(bǔ)血湯可顯著增加老年小鼠肌肉質(zhì)量和力量，而對于對照組的影響則不明顯；

2、理氣補(bǔ)血湯可降低血清中TGF-β1的水平；

3、理氣補(bǔ)血湯可降低小鼠肌肉中Smad及p-Smad的水平，及相應(yīng)的細(xì)胞因子及蛋白質(zhì)的表達(dá)水平。

Conclusion

本研究表明，理氣補(bǔ)血湯可通過調(diào)控TGF-β1/Smad通路的活性，降低肌肉中的TGF-β1水平，從而緩解失神經(jīng)骨骼肌萎縮的癥狀。這一結(jié)果為老年肌肉萎縮的治療提供了新思路，為進(jìn)一步探索其相關(guān)的機(jī)制提供了可行性的理論支持Background

Sarcopeniaisasyndromecharacterizedbythelossofskeletalmusclemassandfunctionwithaging,whichleadstophysicaldisability,frailtyandpoorqualityoflife.TraditionalChinesemedicine(TCM)hasbeenusedforyearstotreatage-relateddisorders,includingsarcopenia.Inthisstudy,weaimedtoevaluatetheeffectivenessofaTCMformula,LiQiBuXueTang(LQBXT),onsarcopeniainagingmice.

Methods

MaleC57BL/6Jmiceaged18-24monthswererandomlydividedintotwogroups:atreatmentgroup(n=10),whichreceivedLQBXTtwicedailyfor4weeks,andacontrolgroup(n=10),whichreceivednotreatment.Musclemass,musclestrength,musclemorphology,andtheexpressionoftransforminggrowthfactor-beta1(TGF-β1)/Smadsignalingpathwaycomponentsinmuscletissueswereevaluated.

Results

Comparedwiththecontrolgroup,thetreatmentgroupshowedasignificantincreaseinmusclemassandstrength.Inaddition,LQBXTreducedserumTGF-β1levels,down-regulatedSmadandphosphorylated(p)-Smadlevels,anddecreasedtheexpressionofrelatedcytokinesandproteinsinskeletalmuscletissues.

Conclusion

TheseresultsprovideevidencethatLQBXTamelioratessarcopeniabymodulatingTGF-β1/SmadsignalingpathwayactivityandreducingTGF-β1levelsinskeletalmuscletissues.Therefore,LQBXTmayrepresentapromisingtherapeuticstrategyforsarcopenia,andfurtherstudiesarewarrantedtoelucidatetheunderlyingmechanismsSarcopeniaisamultifactorialandcomplexconditionthataffectsolderadultsandleadstosignificantdecreasesinmusclemass,strength,andfunction.Astheglobalpopulationcontinuestoage,sarcopeniahasbecomeamajorpublichealthconcernduetoitsimpactonindependence,mobility,andqualityoflife.

Currenttreatmentoptionsforsarcopeniaarelimitedandoftenhaveinsufficientefficacy,highlightingtheneedfornovelandeffectivetherapeuticstrategies.HerbalmedicineshavebeenusedforcenturiesintraditionalChinesemedicinetotreatvariousailments,includingmusclewasting.LQBXTisonesuchherbalformulathathasbeenshowntohavepotentialbenefitsforsarcopenia.

ThefindingsofseveralstudiessuggestthatLQBXTcanimprovemusclestrengthandfunctioninsarcopenicpatients.Inaddition,LQBXThasbeenfoundtoreducethelevelsofinflammatorycytokines,suchasIL-6,TNF-α,andCRP,inolderadults,suggestingthatitmayhaveanti-inflammatorypropertiesthatcouldbenefitsarcopenia.

ThemechanismsbywhichLQBXTexertsitsbeneficialeffectsonsarcopeniaarenotcompletelyunderstood.However,recentstudieshaveshedlightonsomeofthemolecularpathwaystargetedbyLQBXT.Forexample,inaratmodelofsarcopenia,LQBXTwasfoundtodownregulatetheTGF-β1/Smadsignalingpathway,leadingtoadecreaseintheexpressionoffibroticmarkersandanimprovementinmusclemassandfunction.

TGF-β1isacytokinethatisknowntoplayaroleinthedevelopmentofsarcopeniabypromotingmusclefibrosisandmitochondrialdysfunction.TheTGF-β1/SmadsignalingpathwayisactivatedbyTGF-β1bindingtoitsreceptors,leadingtothephosphorylationandactivationofSmadproteinsthatthentranslocateintothenucleusandregulategeneexpression.Inskeletalmuscletissues,activationoftheTGF-β1/Smadsignalingpathwayhasbeenassociatedwithdecreasesinmusclemassandstrength.

Therefore,targetingtheTGF-β1/Smadsignalingpathwaymayrepresentaviabletherapeuticapproachforsarcopenia.LQBXThasbeenshowntoinhibitthispathwayinskeletalmuscletissues,suggestingthatitmayhavepotentialasatherapeuticagentforthetreatmentofsarcopenia.

Inconclusion,LQBXTrepresentsapromisingherbalformulaforthetreatmentofsarcopenia.Itspotentialbenefitsmaybeattributed,atleastinpart,toitsabilitytomodulatetheTGF-β1/SmadsignalingpathwayandreduceTGF-β1levelsinskeletalmuscletissues.FurtherstudiesarewarrantedtoelucidatetheprecisemechanismsofactionofLQBXTandtoevaluateitsefficacyandsafetyinlargerclinicaltrialsSarcopeniaisagrowingconcernastheelderlypopulationincreasesworldwide.Currenttreatmentsforsarcopeniahavelimitedefficacyandoftencomewithsideeffects.Therefore,researchintonaturalcompoundsandherbalformulasthatcanalleviatesymptomsofsarcopeniawithoutadverseeffectsisofgreatinterest.

LQBXTisanherbalformulathathasbeentraditionallyusedtotreatmuscleweaknessandatrophyinChina.RecentstudieshaveshownthatLQBXThaspotentialasatherapeuticagentforsarcopeniathroughitsabilitytomodulatetheTGF-β1/SmadsignalingpathwayandreduceTGF-β1levelsinskeletalmuscletissues.

TheTGF-β1/Smadsignalingpathwayplaysakeyroleinregulatingmusclegrowthandmaintenance.Animbalanceinthispathwayisassociatedwithmusclewasting,whichisahallmarkofsarcopenia.LQBXThasbeenshowntoregulatethispathwaybydownregulatingtheexpressionofTGF-β1anditsdownstreamtargets,includingSmad2andSmad3.

InadditiontoitseffectsontheTGF-β1/Smadpathway,LQBXThasbeenshowntoincreasemusclemassandstrengthinanimalmodelsofsarcopenia.Theseeffectswereattributedtotheformula'sabilitytoincreasetheexpressionofmyosinheavychainandreducethelevelsofatrophy-relatedgenes.

Furthermore,LQBXThasbeenshowntohaveanti-inflammatoryeffectsinskeletalmuscletissue,whichmaycontributetoitsefficacyintreatingsarcopenia.Chronicinflammationisacommonfeatureofsarcopenia,andreducingthisinflammationisanimportantstrategyfor