逍遥散对大鼠阿尔茨海默病模型前额叶皮质PP-2A和GSK-3β的影响

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目的:探讨逍遥散对阿尔茨海默病大鼠模型前额叶皮质相关指标的影响。方法:将清洁级4~5个月龄SD雄性大鼠随机分为4个组,模型组(B组)、西药组(C组)、中药组(D组)分别采用D-半乳糖腹腔注射和A-β1~42peptide双侧海马注射联合造模[用药剂量:D-半乳糖10 mL(100 mg·kg-1),每日1次,连续注射42 d;A-β每侧海马组织1次性注射2μL(10μg)],生理组(A组)仅用等体积生理盐水做相同的造模处理。造模完成后,C、D组每日分别用奥拉西坦溶液0.75 g·kg-1和逍遥散煎剂10.g-1ig干预,1次/d,连续28 d,用药体积均为5 mL·kg-1;A,B组采用等体积的生理盐水ig。ig结束后,4个组分别进行Y迷宫行为学检测,并对比分析。之后断头剥离前额叶皮质送检。结果:B,C,D两组与B组比较,其尝试次数和行为正确率均占明显优势,差异具有统计学意义(尝试次数P<0.05;行为正确率P<0.01);B组与A组比较,尝试次数和行为正确率降低,差异具有统计学意义(尝试次数P<0.05;行为正确率P<0.01);降低C、D组与A组比较差异无统计学意义。免疫组化染色显示,与B组比较,C组和D组PP-2A阳性细胞数量表达均明显增加,而GSK-3β阳性细胞数量表达均明显减少。结论:逍遥散能改善AD大鼠的空间记忆能力,与其能够上调AD大鼠前额叶的PP-2A的表达、抑制前额叶的GSK-3β的表达有关。 Objective: To investigate the effect of Xiaoyaosan on the related index of prefrontal cortex in Alzheimer’s disease rat model. Methods: Male Sprague-Dawley rats aged 4-5 months were randomly divided into four groups: model group (group B), western medicine group (group C) and traditional Chinese medicine group (group D) And A-β1 ~ 42peptide bilateral hippocampal injection combined modeling [Dose: D-galactose 10 mL (100 mg · kg-1), once daily for 42 days; A-β each side of the hippocampus tissue 1 2 μL (10 μg) was injected subcutaneously), and the physiological group (group A) was treated with the same modeling solution with an equal volume of normal saline. After modeling, C and D groups were treated with oxiracetam solution 0.75 g · kg-1 and Xiaoyaosan decoction 10. g-1ig respectively for 1 day / d for 28 consecutive days with a volume of 5 mL · kg-1; group A, B used an equal volume of saline ig. ig after the end of the four groups were Y maze behavior test, and comparative analysis. After decapitation stripping of the anterior cortex for submission. Results: Compared with group B, the number of trials and the correct rate of behavior accounted for significant differences between groups B, C and D (P <0.05 for trial and P <0.01 for correct behavior) The number of trials and the correct rate of behavior decreased. The difference was statistically significant (the number of trials was P <0.05; the correct rate of behavior was P <0.01). There was no significant difference between C and D groups and A group. Immunohistochemical staining showed that compared with group B, the number of PP-2A positive cells in group C and group D were significantly increased, while the number of GSK-3β-positive cells was significantly decreased. Conclusion: Xiaoyaosan can improve the spatial memory ability of AD rats, which is related to its ability to up-regulate the expression of PP-2A in prefrontal cortex and inhibit the expression of GSK-3β in prefrontal cortex.
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