基于TLR4/MyD88/NF-κB信号通路探讨电针对阿尔茨海默病大鼠学习记忆能力的影响  

Dicussion on the effects of electroacupuncture on the learning and memory abilities of Alzheimer’s disease rats based on the TLR4/MyD88/NF-κB signaling pathway

作　　者：徐子绚 宋杰[1] 王平[1] 杜艳军[1] XU Zixuan;SONG Jie;WANG Ping;DU Yanjun(Hubei University of Chinese Medicine,Wuhan 430065,China)

机构地区：[1]湖北中医药大学,武汉430065

出　　处：《中华中医药杂志》2024年第1期186-191,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家中医药管理局国家中医药领军人才支持计划—岐黄学者(No.国中医药人教函[2018]284号);国家中医药管理局“全国名中医传承工作室”建设项目(No.国中医药人教发[2022]5号);国家自然科学基金面上项目(No.82074566)。

摘　　要：目的:观察电针“肾俞”“丰隆”穴对阿尔茨海默病(AD)大鼠学习记忆能力的影响,并基于Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核因子κB(NF-κB)信号通路探讨其作用机制。方法:60只大鼠随机分为假手术组、模型组、补肾组、化痰组、补肾化痰组。除假手术组外,其余组双侧脑室注射β淀粉样蛋白(Aβ)25-35造模。补肾组、化痰组、补肾化痰组分别电针“肾俞”单穴、“丰隆”单穴及“肾俞”“丰隆”双穴。Morris水迷宫(MWM)检测学习记忆能力;HE染色、尼氏染色观察海马病理形态;ELISA检测血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-4、IL-6、IL-10浓度;RT-PCR检测海马TLR4、MyD88、NF-κB p65、TNF-α、IL-1β、IL-6 mRNA表达;Western Blot检测海马TLR4、MyD88、NF-κB p65蛋白表达。结果:与模型组比较,其余各组大鼠平均逃避潜伏期显著减少(P<0.01),平均穿越平台次数显著增加(P<0.01);海马神经元层次清晰,神经元相对表达显著增加(P<0.01);血清TNF-α、IL-1β、IL-6浓度显著减少(P<0.01),IL-4、IL-10浓度显著增加(P<0.01);海马TNF-α、IL-1β、IL-6、TLR4、MyD88、NF-κB p65 mRNA相对表达量显著减少(P<0.05),海马TLR4、MyD88、NF-κB p65蛋白相对表达量显著减少(P<0.01)。结论:电针可改善AD大鼠学习记忆能力,其机制可能与下调TLR4/MyD88/NF-κB信号通路抑制炎症反应有关。Objective:To observe the effects of electroacupuncture(EA)at‘Shenshu’(BL 23)and‘Fenglong’(ST 40)on learning and memory ability in Alzheimer’s disease(AD)rats,and to explore its mechanism based on Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factorκB(NF-κB)signaling pathway.Methods:A total of 60 male SD rats were randomly divided into sham operation,model,tonifying kidney,resolving phlegm and tonifying kidney and resolving phlegm groups.Except for the sham-operation group,the rats in the other groups were injected withβ-amyloid(Aβ)25-35 into bilateral ventricles to establish the model.EA was applied to‘Shenshu’(BL 23),‘Fenglong’(ST 40),‘Shenshu’(BL 23)and‘Fenglong’(ST 40)in the Bushen,Huatan and Bushen Huatan group,respectively.Morris water maze(MWM)was used to detect learning and memory ability.HE staining and Nissl staining were used to observe the pathological morphology of hippocampus.ELISA was used to detect the concentrations of tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-4,IL-6 and IL-10 in serum.The expressions of TLR4,MyD88,NF-κB p65,TNF-α,IL-1βand IL-6 mRNA in hippocampus were detected by RT-PCR.The protein expressions of TLR4,MyD88 and NF-κB p65 in hippocampus were detected by Western Blot.Results:Compared with the model group,the average escape latency of the other groups was significantly reduced(P<0.01),and the average number of platform crossings significantly increased(P<0.01);The hippocampal neuronal hierarchy was clear,and the relative expression of neurons was significantly increased(P<0.01);The serum levels of TNF-α,IL-1βand IL-6 were significantly decreased(P<0.01),and the concentrations of IL-4 and IL-10 were significantly increased(P<0.01);The relative expressions of TNF-α,IL-1β,IL-6,TLR4,MyD88 and NF-κB p65 mRNA in hippocampus were significantly decreased(P<0.05);The relative expressions of TLR4,MyD88,and NF-κB p65 proteins in the hippocampus were significantly decreased(P<0.01).Conclusion:EA can improve the lea

关 键 词：阿尔茨海默病 电针 学习记忆 TLR4/MyD88/NF-κB信号通路 

分 类 号：R245.97[医药卫生—针灸推拿学]