基于TLR4-MyD88-NF-κB信號通路探討電針改善AD模型大鼠學(xué)習(xí)記憶能力的作用機(jī)制

基于TLR4-MyD88-NF-κB信號通路探討電針改善AD模型大鼠學(xué)習(xí)記憶能力的作用機(jī)制

摘要：阿爾茨海默?。ˋD）是一種常見的神經(jīng)退行性疾病，以認(rèn)知和記憶障礙為主要臨床特征。電針作為中醫(yī)傳統(tǒng)療法，已被廣泛應(yīng)用于提高學(xué)習(xí)記憶能力的治療中。本研究通過建立AD模型大鼠，并應(yīng)用電針治療，探討TLR4/MyD88/NF-κB信號通路在電針改善AD模型大鼠學(xué)習(xí)記憶能力中的作用機(jī)制。

方法：將50只雄性SD大鼠隨機(jī)分為正常對照組、AD模型組和電針治療組。AD模型組和電針治療組大鼠均經(jīng)過腹腔注射β-淀粉樣前體蛋白（Aβ1-40）建立AD模型。電針治療組大鼠經(jīng)過電針治療，每天持續(xù)2周。在治療結(jié)束后，使用Morris水迷宮任務(wù)評估大鼠學(xué)習(xí)記憶能力。同時(shí)，采用免疫組織化學(xué)和實(shí)時(shí)熒光定量PCR方法檢測大鼠海馬區(qū)組織中TLR4、MyD88和NF-κB的表達(dá)水平。

結(jié)果：與正常對照組相比，AD模型組大鼠在Morris水迷宮任務(wù)中的逃避時(shí)間延長，而電針治療組大鼠的逃避時(shí)間顯著縮短。組織學(xué)分析顯示，AD模型組大鼠海馬區(qū)TLR4、MyD88和NF-κB的表達(dá)水平明顯增加，而電針治療組大鼠的表達(dá)水平則顯著降低。

結(jié)論：電針治療可顯著改善AD模型大鼠的學(xué)習(xí)記憶能力，通過抑制TLR4/MyD88/NF-κB信號通路的活化，減少炎癥反應(yīng)和神經(jīng)元損傷，從而發(fā)揮其治療作用。這些結(jié)果為電針治療AD提供了新的證據(jù)，并為未來進(jìn)一步研究AD治療的機(jī)制和方法提供了新的思路。

關(guān)鍵詞：阿爾茨海默??；電針；學(xué)習(xí)記憶；TLR4；MyD88；NF-κB信號通路

Abstract:

Alzheimer'sdisease(AD)isacommonneurodegenerativedisordercharacterizedbycognitiveandmemoryimpairments.Electroacupuncture,asatraditionalChinesetherapy,hasbeenwidelyusedinthetreatmentofimprovinglearningandmemoryabilities.Inthisstudy,weestablishedanADmodelinratsandappliedelectroacupuncturetoinvestigatethemechanismofactionbasedontheTLR4/MyD88/NF-κBsignalingpathwayinimprovinglearningandmemoryabilitiesintheADmodelrats.

Methods:

FiftymaleSDratswererandomlydividedintoanormalcontrolgroup,anADmodelgroup,andanelectroacupuncturetreatmentgroup.TheADmodelgroupandelectroacupuncturetreatmentgroupratswereinducedADmodelbyintraperitonealinjectionofβ-amyloidprecursorprotein(Aβ1-40).Theelectroacupuncturetreatmentgroupratsreceivedelectroacupuncturetreatmentdailyfor2weeks.Afterthetreatment,thelearningandmemoryabilitiesofratswereevaluatedusingtheMorriswatermazetest.Meanwhile,theexpressionlevelsofTLR4,MyD88,andNF-κBinthehippocampustissuesofratsweredetectedbyimmunohistochemistryandreal-timefluorescencequantitativePCR.

Results:

Comparedwiththenormalcontrolgroup,theescapetimeintheMorriswatermazetestwasprolongedintheADmodelgrouprats,whileitwassignificantlyshortenedintheelectroacupuncturetreatmentgrouprats.HistologicalanalysisshowedthattheexpressionlevelsofTLR4,MyD88,andNF-κBinthehippocampusofADmodelgroupratsweresignificantlyincreased,whiletheexpressionlevelsintheelectroacupuncturetreatmentgroupratsweresignificantlydecreased.

Conclusion:

ElectroacupuncturetreatmentcansignificantlyimprovelearningandmemoryabilitiesinADmodelratsbyinhibitingtheactivationofTLR4/MyD88/NF-κBsignalingpathway,reducinginflammation,andneuronaldamage.ThesefindingsprovidenewevidenceforthetreatmentofADwithelectroacupunctureandoffernewperspectivesforfurtherresearchonthemechanismsandmethodsofADtreatmentinthefuture.

Keywords:Alzheimer'sdisease;electroacupuncture;learningandmemory;