柚皮苷通过调节小胶质细胞极化对 APPswe / PS1dE9 双转基因小鼠的认知功能影响
作者:
作者单位:

1.河南科技大学医学院,河南 洛阳 471023; 2.杭州医学院,杭州 310051; 3.河南科技大学第一附属医院, 河南 洛阳 471023

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R-33


Naringin mediates the cognitive function of APPswe / PS1dE9 transgenic mice by regulating microglia polarization
Author:
Affiliation:

1.Medical College, Henan University of Science and Technology, Luoyang 471023, China. 2. Hangzhou Medical College, Hangzhou 310051. 3. the First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471023

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    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、 iNOS、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。

    Abstract:

    Objective To investigate the regulatory effects of naringin on microglia polarization and Aβ clearance and cognition in APPswe / PS1dE9 transgenic mice. Methods Three-month-old male APPswe / PS1dE9 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 Aβ and the phagocytic effect of activated microglia cells on Aβ. Results Compared with the control group, APPswe / PS1dE9 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, iNOS, 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 / PS1dE9 mice (P< 0. 05). Furthermore, the Aβ-positive region was significantly elevated in the cerebral cortex and hippocampus of APPswe / PS1dE9 mice (P< 0. 05). Compared with the model group, naringin administration markedly increased the discrimination index in APPswe / PS1dE9 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 Aβ by microglia (P< 0. 05). There was no significant difference in liver and kidney function parameters among the groups (P> 0. 05). Conclusions Naringin can promote microglial polarization from the M1-type towards the M2-type, enhance Aβ phagocytosis by activated microglia, and subsequently improve cognition in mice.

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王 贝,赵雨航,王乐伟,潘顺基,石 见,王冬梅.柚皮苷通过调节小胶质细胞极化对 APPswe / PS1dE9 双转基因小鼠的认知功能影响[J].中国比较医学杂志,2021,31(2):1~7.

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  • 收稿日期:2020-06-16
  • 在线发布日期: 2021-04-07
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