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。
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.
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