黄连素对阿尔兹海默症大鼠学习记忆功能及海马组织GSK3β、p-Tau蛋白表达的影响

Effects of berberine on learning and memory function and expression of GSK3β and p-Tau protein in hippocampus of Alzheimer’s rats

目的探究不同剂量黄连素对阿尔兹海默症大鼠学习和认知功能的影响,以及黄连素对丝氨酸蛋白激酶3β(serine protein kinase 3β,GSK3β)、p-Tau蛋白表达的影响。方法大鼠分为假手术组、模型组、黄连素低中高剂量组,除假手术组外,其余各组采用腹腔注射D-半乳糖联合Aβ25-35脑注射的方法建立阿尔兹海默症模型大鼠,药物干预4周后,检测Morris水迷宫实验、海马组织GSK3β、p-Tau蛋白表达量。结果与模型组相比,黄连素治疗组大鼠逃避潜伏期、游泳总路程不同程度降低,穿越目标区域次数增加,其中黄连素高剂量组降低最显著(P<0.01,P<0.05)。黄连素组海马GSK3β、p-Tau蛋白表达较模型组显著降低,高剂量组降低最显著(P<0.01)。结论黄连素能改善阿尔兹海默症大鼠学习和记忆能力,其中150 mg/kg黄连素对善阿尔兹海默症大鼠治疗效果优于50 mg/kg及100 mg/kg,其机制与黄连素降低大鼠海马组织GSK3β、p-Tau蛋白表达有关。

Objective To investigate the effects of different doses of berberine on learning and cognitive function in rats with Alzheimer’s disease,and the effects of berberine on the expression of GSK3 beta and p-Tau protein.Methods Rats were divided into sham-operated group,model group and berberine low,medium and high dose groups.Except sham-operated group,the other groups were established Alzheimer’s disease model rats by intraperitoneal injection of D-galactose combined with intracerebral injection of Aβ25-35.After 4 weeks of drug intervention,Morris water maze test,expression of GSK3βand p-Tau protein in hippocampus tissue were detected.Results Compared with the model group,the escape latency and total swimming distance of rats in Berberine treatment group decreased in varying degrees,and the number of times of crossing the target area increased,especially in the berberine high dose group(P<0.01).The expression of GSK3βand p-Tau protein in hippocampus of berberine group was significantly lower than that of model group,and the lowest was in high dose group(P<0.01,P<0.05).Conclusion Berberine can improve the learning and memory ability of rats with Alzheimer’s disease.The effect of berberine 150 mg/kg on rats with Alzheimer’s disease is better than that of 50 mg/kg or 100mg/kg.The mechanism is related to the decrease of GSK3βand p-Tau protein expression in rat hippocampus by berberine.