中医药导报2023,Vol.29Issue(12):19-23,52,6.DOI:10.13862/j.cn43-1446/r.2023.12.004
槲皮素调控TLR4/NF-κB通路对阿尔茨海默病大鼠认知功能障碍及海马神经元损伤的影响
Influences of Quercetin on Cognitive Dysfunction and Hippocampal Neuronal Damage in Rats with Alzheimer's Disease Through Modulation of TLR4/NF-κB Pathway
摘要
Abstract
Objective:To investigate the influences of quercetin(Que)on cognitive dysfunction and hippocampal neuronal damage in Alzheimer's disease(AD)rats by modulating Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)pathway.Methods:Totally 60 rats were randomly divided into sham-operation group(n=10)and modeling group(n=50).The modeling group was constructed by intracerebral injection of Aβ1-42 for AD rat model,and the successfully modeled rats were randomly grouped into AD group,Que low(Que-L,50 mg/kg)dose group,Que medium(Que-M,100 mg/kg)dose group,Que high dose(Que-H,200 mg/kg)groups and Que-H+LPS(TLR4 acti-vator)group(200 mg/kg Que+0.1 mg/kg LPS),10 rats in each group.After the end of the intervention,Morris water maze experiment was applied to detect spatial learning memory ability in rats.ELISA was applied to detect serum levels of tumor necrosis factor-α(TNF-α)and interleukin(IL)-1 β.HE staining was applied to observe histopathological changes in rat hippocampus.TUNEL staining was applied to detect apoptotic changes.Western blotting was used to detect the expression levels of TLR4 and p-NF-κB p65/NF-κB p65 in hippocampal tissues.Results:The AD group showed lower number of crossing the original platform than sham-operated group,while higher escape latency,serum TNF-α,serum IL-1β,apoptosis rate,TLR4 expression,and p-NF-κB p65/NF-κB p65 than sham-operated group,with statistically significant differences(P<0.05).The Que-L,Que-M and Que-H groups showed higher number of crossing the original platform than AD group,while lower escape latency,serum TNF-α,serum IL-1β,apoptosis rate,TLR4 expression,and p-NF-κB p65/NF-κB p65 than AD group,with statistically significant differences(P<0.05).And there was a dose-dependence.The Que-H+LPS group showed lower number of crossing the original platform than Que-H group,while higher escape latency,serum TNF-α,serum IL-1 β,apoptosis rate,TLR4 expression,and p-NF-κB p65/NF-κB p65 than Que-H group,with statistically significant differences(P<0.05).Conclusion:Que can improve cognitive dysfunction and hippocampal neuronal damage in AD rats,which may be related to the inhibition of TLR4/NF-κB pathway.关键词
阿尔茨海默病/槲皮素/TLR4/NF-κB通路/认知功能障碍/海马神经元损伤/大鼠Key words
Alzheimer's disease/Quercetin/TLR4/NF-κB pathway/cognitive dysfunction/hippocampal neuronal damage/rat分类
医药卫生引用本文复制引用
王玲,杜潇,祝华莲,吴萍..槲皮素调控TLR4/NF-κB通路对阿尔茨海默病大鼠认知功能障碍及海马神经元损伤的影响[J].中医药导报,2023,29(12):19-23,52,6.基金项目
成都中医药大学附属医院科研项目(18PY26) (18PY26)