补肾益志方通过β淀粉样蛋白和tau蛋白调节大鼠阿尔茨海默病的实验研究

Experimental study of Bushen Yizhi Recipe regulating Alzheimer's disease in rats throughβ-amyloid and tau proteins

目的观察补肾益志方对阿尔茨海默病(Alzheimer's disease,AD)大鼠模型的作用及其对β淀粉样蛋白(β-amyloid protein,Aβ)和tau蛋白的影响。方法通过Aβ25-35建立AD大鼠模型,给予补肾益志方(13.00、6.50、3.25 g/kg)、多奈哌齐治疗,设为假手术组、模型组、补肾益志方低剂量组、补肾益志方中剂量组、补肾益志方高剂量组、阳性组。Morris水迷宫实验检测大鼠的逃避潜伏期、目标象限游泳时间、游泳总路程及自主活动时间;HE染色法观察大鼠海马组织的病理变化;ELISA法、Western blot法检测海马组织中Aβ40、Aβ42、磷酸化tau蛋白(p-tau)的含量及蛋白表达。结果与假手术组相比,模型组逃避潜伏期、目标象限游泳时间、游泳总路程和自主活动时间均显著升高(P<0.05);与模型组相比,补肾益志方低、中、高剂量组逃避潜伏期、目标象限游泳时间、游泳总路程和自主活动时间均显著降低(P<0.05)。模型组海马损伤最严重,补肾益志方低、中、高剂量组海马均有明显好转,补肾益志方高剂量组海马与假手术组最接近。模型组海马中Aβ40、Aβ42、p-tau的含量和蛋白表达均显著高于假手术组(P<005),补肾益志方低、中、高剂量组海马Aβ40、Aβ42、p-tau的含量和蛋白表达均显著低于模型组(P<005)。结论补肾益志方可改善AD大鼠的学习记忆能力,其机制与抑制Aβ和tau蛋白有关。

Objective To observe the effect of Bushen Yizhi Recipe on Alzheimer's disease(AD)rat model and its effect onβ-amyloid protein(Aβ)and tau protein.Methods AD rat model was established by Aβ25-35,and treated with Bushen Yizhi Recipe(13.00,6.50,3.25 g/kg)and Donepezil.Sham operation group,model group,Bushen Yizhi Recipe low-dose group,Bushen Yizhi Recipe medium-dose group,Bushen Yizhi Recipe high-dose group and positive group were set up in the experiment.Morris water maze experiment was used to detect the escape latency,target quadrant swimming time,total swimming distance and free activity time of rats.The pathological changes of rat hippocampal tissue were observed by HE staining.The content and protein expression of Aβ40,Aβ42 and phosphorylated tau(p-tau)in hippocampal tissue were detected by ELISA and Western blot.Results Compared with the sham operation group,the escape latency,target quadrant swimming time,total swimming distance and free activity time of the model group were significantly increased(P<005).Compared with the model group,the escape latency,target quadrant swimming time,total swimming distance and free activity time of rats in the Bushen Yizhi Recipe low-dose,medium-dose,high-dose groups were significantly reduced(P<0.05).The hippocampal injury of rats in the model group was the most serious,the hippocampal injury of rats was significantly improved in Bushen Yizhi Recipe low-dose,medium-dose,high-dose groups,and the hippocampal injury of rats in the Bushen Yizhi Recipe high-dose group was the closest to that in the sham operation group.The content and protein expression of Aβ40,Aβ42,p-tau were significantly higher than those in the sham operation group(P<005).The content and protein expression of Aβ40,Aβ42,p-tau were significantly lower than those in the model group in Bushen Yizhi Recipe low-dose,medium-dose,high-dose groups(P<005).Conclusion Bushen Yizhi Recipe can improve the learning and memory ability of AD rats,and its mechanism may be related to the inhibition of Aβand tau proteins.