目的研究三七皂苷Rg1对阿尔茨海默病(Alzheimer’s disease,AD)模型大鼠空间学习记忆能力和磷酸化tau蛋白的作用及机制。方法 SD大鼠左侧脑室Aβ25-35注射复制AD模型,分别用低(25mg/kg)、中(50mg/kg)、高剂量(100mg/kg)的三七皂苷Rg1灌胃,2次/d,4周后进行Morris水迷宫实验检测学习记忆能力,并通过免疫印迹、免疫组织化学方法,检测各组大鼠海马tau蛋白磷酸化水平及分布的变化。结果侧脑室注射Aβ25-35后,模型大鼠学习记忆能力显著低于正常对照大鼠;免疫印迹法检测结果显示,海马tau蛋白苏氨酸231位点磷酸化(PT231)水平明显增加,非磷酸化水平明显下降;形态学检测结果显示,模型大鼠海马DG区、CA1区和CA3区的PT231水平明显增加。中剂量的三七皂苷Rg1干预能显著改善模型大鼠在Morris水迷宫中学习记忆的能力;3种剂量的三七皂苷Rg1均能降低其海马DG、CA1、CA3区的tau蛋白PT231水平,且3种剂量之间的差异无统计学意义。结论三七皂苷Rg1能改善Aβ25-35诱导的模型大鼠AD样空间学习记忆能力障碍及降低海马tau蛋白磷酸化水平。
Objective To study the effects of panax notoginsen gsaponins Rg1 on the model of Alzheimer's Disease(AD)and related mechanism.Methods AD model was established by injection of Aβ25-35 in the left lateral ventricles of SD rats.These rats were treated with low(25mg/kg),medium(50mg/kg)and high(100mg/kg)dose of panax notoginsen gsaponins Rg1,twice a day.Then the Morris water maze was used to detect the ability of learning and memory,Western blotting was adopted to detect hyperphosphorylation tau protein,and immunohistochemical methods to analyze its distribution in the left hippocampus 4 weeks after the treatment.Results The learning and memory ability of AD rat model was inferior to the normal rats with the phosphorylation level of tau protein at Thr231site(PT231)increased and the nonphosphorylation level of tauprotein decreased.PT231 level of AD rat model increased markedly in region of DG,CA1 and CA3 of the hippocampus in morphology.Middle dose of panax notoginseng saponins Rg1 could effectively improve the ability of learning and memory.The three doses of panax notoginsen gsaponins Rg1 could decrease the level of PT231 and there was no significant difference among them.Conclusion Prescription of panax notoginsen gsaponins Rg1 can improve the ability of learning and memory and decrease the hyperphosphorylation of tau protein of AD rat model induced by Aβ25-35.