文章摘要
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
Study on the mechanism of probiotics improving the cognitive function of AD mice by regulating microglia polarization
投稿时间:2025-07-05  修订日期:2025-07-05
DOI:
中文关键词: 益生菌  小胶质细胞极化  阿尔茨海默病
英文关键词: Probiotics  Microglia polarization  Alzheimer""s disease
基金项目:
作者单位邮编
李丹 新疆医科大学附属中医医院 830000
孟新玲* 新疆医科大学附属中医医院 830000
张玉洁 新疆医科大学附属中医医院 
刘婷 新疆医科大学附属中医医院 
马娜 新疆医科大学附属中医医院 
房江山 新疆医科大学附属中医医院 
马海者 新疆医科大学附属中医医院 
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中文摘要:
      目的:观察益生菌对AD大鼠认知功能的改变和小胶质细胞极化的影响,初步探索其作用机制,为益生菌合理使用提供理论依据。方法:将90只雄性大鼠分为3组:假手术组(n=30)、模型组、模型+益生菌组(n=30),假手术组(n=30)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:(1)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,正确通道选择能力显著升高(P<0.05);(2)假手术组、模型组和模型+益生菌组的海马组织中IBA1蛋白进行观察,模型组海马组织IBA1蛋白表达均显著升高,差异具有统计学意义(P<0.01),对皮质区、海马区通过激光共聚焦显微镜观察显示:皮质区、海马区M1型小胶质细胞与假手术组比较,模型组、益生菌组表达显著增多,且两组组间比较差异均具有统计学意义;相较于模型组,益生菌干预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,差异具有统计学意义;皮质区、海马区M1/M2型小胶质细胞比值益生菌组较模型组下降,差异具有统计学意义;(3)益生菌组小胶质细胞对Aβ吞噬作用显著强于模型组,差异具有统计学意义(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型小胶质细胞细胞转化。
英文摘要:
      Objective: To observe the changes in cognitive function and microglial polarization in AD rats treated with probiotics, and to preliminarily explore its mechanism of action, providing a theoretical basis for the rational use of probiotics. Methods: Ninety male rats were divided into three groups: sham operation group (n=30), model group, and model + probiotics group (n=30). The sham operation group was injected with sterile water into the bilateral hippocampal CA1 region of rats, while the model group was injected with Aβ1-42 into the bilateral hippocampal CA1 region. The model + probiotics group was injected with Aβ1-42 into the bilateral hippocampal CA1 region and treated with probiotics by gavage. The cognitive function of each group of rats was evaluated. The changes of microglia (M1 and M2) in the cortex and hippocampus were detected by immunofluorescence. Primary microglia were isolated and cultured, and the expression of IBA1 was observed by immunofluorescence, and the phagocytic function was determined. Results: (1) The correct channel selection ability of the model + probiotics group was significantly enhanced in the Y-maze test compared with the model group, and the correct channel selection ability was significantly increased (P < 0.05); (2) The expression of IBA1 protein in the hippocampus of the sham operation group, model group and model + probiotics group was observed. The expression of IBA1 protein in the hippocampus of the model group was significantly increased, and the difference was statistically significant (P < 0.01). The laser confocal microscope was used to observe the cortex and hippocampus, showing that the expression of M1-type microglia in the cortex and hippocampus of the model group and probiotics group was significantly increased compared with the sham operation group, and the difference was statistically significant. Compared with the model group, the probiotics intervention group showed a significant increase in the number of M2-type microglia in the cortex and hippocampus, and the difference was statistically significant. The ratio of M1/M2-type microglia in the cortex and hippocampus of the probiotics group was significantly lower than that of the model group, and the difference was statistically significant; (3) The phagocytic function of microglia in the probiotics group was significantly stronger than that in the model group, and the difference was statistically significant (P < 0.05). Conclusion: Probiotics can improve the spatial exploration ability and working memory ability of rats, and enhance the phagocytic function of microglia. The mechanism may be to inhibit the transformation of M1 to M2-type microglia.
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