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机构地区:[1]成都中医药大学,成都610072
出 处:《中药药理与临床》2014年第4期98-102,共5页Pharmacology and Clinics of Chinese Materia Medica
基 金:"重大新药创制"科技重大专项(2013ZX09103002-008)
摘 要:目的:考察乌芩健脑方对Aβ海马注射致痴呆模型大鼠海马细胞周期素依赖性蛋白激酶5(cyclin-dependent kinases-5,CDK5)和糖原合成激酶3(glycogen synthase kinase-3,GSK-3)表达的影响。方法:用聚集状态的Aβ25-35大鼠双侧海马注射建立AD模型,药物干预后,采用Morris水迷宫评价大鼠学习记忆能力,采用免疫组化的方法检测大鼠海马CDK和GSK-3的表达和平均光密度。结果:乌芩健脑方18.48g/kg、9.24 g/kg和4.63 g/kg三个剂量组能显著缩短逃跑潜伏期和第三象限时间,延长第一相限时间和平台停留时间的作用,与模型对照组比较有显著的统计学意义;乌芩健脑方18.48g/kg和9.24 g/kg剂量组海马区CDK5表达较模型对照组显著降低,18.48g/kg、9.24 g/kg和4.63 g/kg三个剂量海马GSK-3的表达均较模型对照组表达显著降低,有显著的统计学意义。结论:乌芩健脑方具有较好的改善痴呆大鼠模型学习记忆功能的作用,并能显著抑制海马区CDK5和GSK-3的异常高表达,提示其抗AD的作用机制可能与通过抑制异常高表达的cdk5和GSK-3,阻止tau蛋白的过度磷酸化有关。Objective: To explore effects of Wuqinjiannao Fang ( Radix Polygoni Multiflofi Praeparata cum Succo Glycines Sotae and Radix Scutel- laria Brain-strengthening Decoction) on expression of cyclin-dependent kinases-5 and glycogen synthase kinase-3 in Alzheimer disease (AD) rats. Methods: Rats were induced by injecting agglomerate Aβ25-35 into bilateral hippocampus. After medication intervention, the learning and memory ability of AD rats was evaluated by Morris water-maze, and expression and average optical density of CDK5 and GSK-3 in hippo- campus were tested by immunohistochemistry. Results: Compared with vehicle control group, the latent period of escaping and the third quadrant time of medication groups of Wu Qin Jian Nao Fang in dose of 18.48g/kg,9.24 g/kg and 4.63 g/kg were significantly shortened, and the first quadrant time and platform residence time were significantly prolonged (P 〈 0.05) ; CDK5 of groups in dose of 18.48g/kg and 9.24 g/kg were significantly decreased ; and GSK-3 of all medicated groups were significantly decreased ( P 〈 0.05 ). Conclusion: Wuqin-jiannao Fang can improve learning and memory abilities of AD rats, and significantly inhibit expression of CDK5 and GSK-3, which presents that the decoration may anti-AD by inhibiting CDK5 and GSK-3 to prevent over phosphorylation of tan protein.
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