益生菌通过调节小胶质细胞极化改善AD大鼠认知功能的机制研究

李丹,孟新玲,张玉洁,刘婷,马娜,房江山,马海者

神经损伤与功能重建 ›› 2026, Vol. 21 ›› Issue (9) : 497-502.

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神经损伤与功能重建 ›› 2026, Vol. 21 ›› Issue (9) : 497-502. DOI: 10.16780/j.cnki.sjssgncj.20241209
论著

益生菌通过调节小胶质细胞极化改善AD大鼠认知功能的机制研究

  • 李丹,孟新玲,张玉洁,刘婷,马娜,房江山,马海者
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Research on the Mechanism by Which Probiotics Improve Cognitive Function in AD Rats through Regulating Microglial Polarization

  • LI Dan, MENG Xinling, ZHANG Yujie, LIU Ting, MA Na, FANG Jiangshan, MA Haizhe
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摘要

目的:观察益生菌对AD大鼠认知功能的改变,初步探索其作用机制。方法:将90只雄性大鼠分为假手术组、模型组、(模型+益生菌)组各30只,假手术组于大鼠双侧海马CA1区注射无菌水,模型组于大鼠双侧海马CA1区注射Aβ1-42,(模型+益生菌)组于大鼠双侧海马CA1区注射Aβ1-42并使用益生菌灌胃。对每组大鼠的认知进行评价,使用免疫荧光检测皮质区、海马区小胶质细胞(M1和M2)变化,原代分离培养小胶质细胞,免疫荧光观察IBA1的表达,并对吞噬作用进行测定。结果:(模型+益生菌)组较模型组Y臂迷宫检测中正确通道的选择能力显著增强,正确通道选择能力升高(P<0.05);与假手术组比较,模型组及(模型+益生菌)组的海马组织IBA1蛋白表达均显著升高(P<0.01),模型组、(模型+益生菌)组对比差异无统计学意义(P>0.05)。与假手术组比较,模型组、(模型+益生菌)组的皮质区、海马区M1型小胶质细胞表达增多(P<0.05);相较于模型组,(模型+益生菌)组在皮质区和海马区呈现出M2型小胶质细胞数量显著升高的现象(P<0.05),三组之间TH17差异具有统计学意义(P<0.05),Treg及Th17/Treg差异无统计学意义;皮质区、海马区M1/M2型小胶质细胞比值下降(P<0.05);(模型+益生菌)组小胶质细胞对Aβ吞噬作用显著强于模型组(P<0.05)。结论:益生菌可改善大鼠空间探索能力和工作记忆能力,并增强小胶质细胞的吞噬功能,其机制可能是抑制M1向M2型小胶质细胞转化。

Abstract

Objective: To observe the effects of probiotics on cognitive function changes in Alzheimer's disease (AD) rats, and to preliminarily explore its underlying mechanism. Methods: Ninety male rats were divided into three groups: sham-operated group, model group, and (model+probiotics) group, with 30 rats in each group. In the sham-operated group, sterile water was injected into the bilateral hippocampal CA1 regions of the rats. In the model group, Aβ1-42 was injected into the same regions. In the (model +probiotics) group, Aβ1-42 was injected into the bilateral hippocampal CA1 regions, followed by probiotic gavage. Cognitive function was evaluated in each group of rats. Immunofluorescence was used to detect changes in microglial cells (M1 and M2) in the cortical and hippocampal regions. Primary microglial cells were isolated and cultured, and the expression of IBA1 was observed using immunofluorescence, along with the measurement of phagocytosis. Results: The (model+probiotics) group exhibited significantly enhanced correct channel selection ability in the Y-maze test compared to the model group, with an increase in correct channel selection ability (P<0.05). Compared with the sham-operated group, the expression of IBA1 protein in the hippocampal tissue was significantly elevated in both the model group and the (model+probiotics) group (P<0.01), with no statistically significant difference between the model group and the (model+probiotics) group (P>0.05). Compared with the sham-operated group, the expression of M1-type microglial cells increased in the cortical and hippocampal regions of both the model group and the (model + probiotics) group (P<0.05). Compared with the model group, the (model+probiotics) group showed a significant increase in the number of M2-type microglial cells in the cortical and hippocampal regions (P<0.05), along with a decrease in the M1/M2 microglial cell ratio in these regions (P<0.05). Additionally, the phagocytic activity of microglial cells against Aβ was significantly stronger in the (model+probiotics) group than in the model group (P<0.05). There was a statistically significant difference in TH17 levels among the three groups (P<0.05), whereas no statistically significant differences were observed in Treg levels or the Th17/Treg ratio. Conclusion: Probiotics can improve spatial exploration ability and working memory capacity in rats and enhance the phagocytic function of microglial cells. The mechanism may involve inhibiting the conversion of M1-type to M2-type microglial cells.

关键词

益生菌;小胶质细胞极化;阿尔茨海默病 化;外部验证

Key words

probiotics; microglia polarization; Alzheimer's disease

引用本文

导出引用
李丹,孟新玲,张玉洁,刘婷,马娜,房江山,马海者. 益生菌通过调节小胶质细胞极化改善AD大鼠认知功能的机制研究[J]. 神经损伤与功能重建. 2026, 21(9): 497-502 https://doi.org/10.16780/j.cnki.sjssgncj.20241209
LI Dan, MENG Xinling, ZHANG Yujie, LIU Ting, MA Na, FANG Jiangshan, MA Haizhe. Research on the Mechanism by Which Probiotics Improve Cognitive Function in AD Rats through Regulating Microglial Polarization[J]. Neural Injury and Functional Reconstruction. 2026, 21(9): 497-502 https://doi.org/10.16780/j.cnki.sjssgncj.20241209

基金

新疆维吾尔自治区自然科学基金项目(丰富环境通过调控辅助性T细胞17/调节性T细胞平衡治疗阿尔茨海默病的研究,No. 2022D01C161);2022年新疆维吾尔自治区重大专项课题(新疆AD精准化防治方案真实世界大样本循证优化研究,No. 2022A03019-1-5);2023年第二批“天山英才”培养计划-科技创新领军人才项目(从T细胞介导免疫失衡角度探索阿尔茨海默病发病机制和防控,No. 2023TSYCLJ0029)

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