摘要
目的探究柚皮苷(naringin)对APPswe/PS1dE9双转基因小鼠小胶质细胞极化的调节效应及该效应对Aβ聚集和认知功能的影响。方法3月龄APPswe/PS1dE9转基因雄性小鼠随机分为模型组(APPswe/PS1dE9)和柚皮苷治疗组(APPswe/PS1dE9+柚皮苷100 mg/(kg·d)),选择年龄体重匹配同窝非转基因小鼠作为阴性对照组和柚皮苷单独给药组(柚皮苷100 mg/(kg·d)),对照组及模型组给予常规的标准鼠粮,APPswe/PS1dE9+柚皮苷组和柚皮苷单独给药组在常规标准鼠粮中加入100 mg/(kg·d)的柚皮苷治疗16周。新物体识别实验检测小鼠非空间短期记忆能力;酶联免疫吸附法检测柚皮苷对小鼠肝肾功能的影响;q-PCR检测小鼠脑组织中小胶质细胞M1型和M2型标记物的表达;免疫荧光染色检测活化小胶质细胞对Aβ的吞噬作用以及Aβ的含量。结果与对照组相比,模型组小鼠新物体识别实验中识别指数显著降低(P<0.05),脑组织M1型标记物(CD16、TNF-α、i NOS、MCP-1)的mRNA表达水平均显著增加(P<0.05),而M2型标记物(CD206、TGF-β、Arg1、YM-1)的mRNA表达均显著降低(P<0.05),大脑皮层和海马的Aβ阳性区域明显增加(P<0.05)。与模型组相比,柚皮苷治疗组小鼠识别指数显著增加(P<0.05),M1型标记物mRNA表达水平均显著降低(P<0.05),M2型标记物mRNA表达均显著增加(P<0.05),促进小胶质细胞对Aβ的吞噬,Aβ免疫阳性区域显著减少(P<0.05)。各组之间小鼠肝肾功能各参数值无显著性差异(P>0.05)。结论柚皮苷通过调节小胶质细胞M1向M2的极化,进而促进活化的小胶质细胞对Aβ的吞噬,最终改善小鼠认知。
Objective To investigate the regulatory effects of naringin on microglia polarization and Aβclearance and cognition in APPswe/PS1 dE9 transgenic mice.Methods Three-month-old male APPswe/PS1 dE9 transgenic mice were randomly assigned to two groups:the model group and the naringin treated group(100 mg/(kg·d)).Non-transgenic mice were selected as the negative Control group and the naringin alone group(100 mg/(kg·d)).The mice were matched in age and weight.Mice in the negative control group and model group were given a conventional standard diet,whereas those in the naringin treatment group and naringin alone group were given a conventional standard diet containing 100 mg/(kg·d)naringin for 16 weeks.The novel object recognition test was performed to assess cognitive function.The effects of naringin on liver and kidney function in mice were assessed by enzyme-linked immunosorbent assays.The expression of M1-type and M2-type microglial markers was examined by quantitative real-time PCR.Immunofluorescence staining was conducted to determine the content of Aβand the phagocytic effect of activated microglia cells on Aβ.Results Compared with the control group,APPswe/PS1 dE9 mice exhibited a significantly decreased discrimination index in the novel object recognition test(P<0.05).The mRNA expression level of M1-type markers(CD16,TNF-α,i NOS,MCP-1)was remarkably upregulated(P<0.05),whereas the mRNA expression of M2-type markers(CD206,TGF-β,Arg1,YM-1)was significantly downregulated in the brains of APPswe/PS1 dE9 mice(P<0.05).Furthermore,the Aβ-positive region was significantly elevated in the cerebral cortex and hippocampus of APPswe/PS1 dE9 mice(P<0.05).Compared with the model group,naringin administration markedly increased the discrimination index in APPswe/PS1 dE9 mice(P<0.05),restored the normal expression of M1-type and M2-type markers in brain tissues(P<0.05),reduced the positive area of Aβ,and promoted the phagocytosis of Aβby microglia(P<0.05).There was no significant difference in liver and kidney functi
作者
王贝
赵雨航
王乐伟
潘顺基
石见
王冬梅
WANG Bei;ZHAO Yuhang;WANG Lewei;PAN Shunji;SHI Jian;WANG Dongmei(Medical College,Henan University of Science and Technology,Luoyang 471023,China;Hangzhou Medical College,Hangzhou 310051;the First Affiliated Hospital of Henan University of Science and Technology,Luoyang 471023)
出处
《中国比较医学杂志》
CAS
北大核心
2021年第2期1-7,共7页
Chinese Journal of Comparative Medicine
基金
国家自然科学基金(U1804174,81601225)
河南省高校科技创新人才支持计划(20HASTIT044)
河南省重点研发与推广专项(科技攻关)项目(192102310081)
河南省自然科学基金(162300410103)。
关键词
柚皮苷
认知
小胶质细胞极化
神经炎症
naringin
cognitive
microglial polarization
neuroinflammation
