基于TLR4-MyD88-NF-κB信号通路探讨电针改善AD模型大鼠学习记忆能力的作用机制

基于TLR4-MyD88-NF-κB信号通路探讨电针改善AD模型大鼠学习记忆能力的作用机制

摘要：阿尔茨海默病（AD）是一种常见的神经退行性疾病，以认知和记忆障碍为主要临床特征。电针作为中医传统疗法，已被广泛应用于提高学习记忆能力的治疗中。本研究通过建立AD模型大鼠，并应用电针治疗，探讨TLR4/MyD88/NF-κB信号通路在电针改善AD模型大鼠学习记忆能力中的作用机制。

方法：将50只雄性SD大鼠随机分为正常对照组、AD模型组和电针治疗组。AD模型组和电针治疗组大鼠均经过腹腔注射β-淀粉样前体蛋白（Aβ1-40）建立AD模型。电针治疗组大鼠经过电针治疗，每天持续2周。在治疗结束后，使用Morris水迷宫任务评估大鼠学习记忆能力。同时，采用免疫组织化学和实时荧光定量PCR方法检测大鼠海马区组织中TLR4、MyD88和NF-κB的表达水平。

结果：与正常对照组相比，AD模型组大鼠在Morris水迷宫任务中的逃避时间延长，而电针治疗组大鼠的逃避时间显著缩短。组织学分析显示，AD模型组大鼠海马区TLR4、MyD88和NF-κB的表达水平明显增加，而电针治疗组大鼠的表达水平则显著降低。

结论：电针治疗可显著改善AD模型大鼠的学习记忆能力，通过抑制TLR4/MyD88/NF-κB信号通路的活化，减少炎症反应和神经元损伤，从而发挥其治疗作用。这些结果为电针治疗AD提供了新的证据，并为未来进一步研究AD治疗的机制和方法提供了新的思路。

关键词：阿尔茨海默病；电针；学习记忆；TLR4；MyD88；NF-κB信号通路

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;