中文摘要：

目的探讨人参皂苷Rg1是否通过调节GSK-3β/PP2A活性而减轻凝聚态A艮。诱导的胎鼠皮层神经元Tau蛋白过度磷酸化。方法选用孕期（18±2）d的SD大鼠，分离纯化胎鼠皮层神经元。实验分为阴性对照组、模型组、LiCl处理组、Rg1预处理组。阴性对照组不加任何处理因素；模型组用20μmol／L哦。作用于皮层神经元12h；LiCl处理组用10mmol／L LiCl和20μmol／L Aβ25-35共同作用于皮层神经元12h；Rg1预处理组分别用5、10、20、40、80μmol／L Rg1预处理皮层神经元24h，再加入20μmol／L Aβ25-35作用12h。通过免疫印迹法和免疫细胞化学染色法检测皮层神经元Tau蛋白磷酸化水平、总Tau蛋白水平和糖原合成酶3β（GSK-3β）表达水平，通过非放射性免疫法检测皮层神经元蛋白磷酸酯酶2A（PP2A）活性。结果模型组Tau蛋白在Ser^396、Ser^199/202和Thr^231位点的磷酸化水平、总Tau蛋白水平和GSK-3p的蛋白表达水平均增加，但PP2A的活性不受影响；LiCl处理组和Rg1预处理组，Tau蛋白在Ser^396、Ser^396/202和Thr^231位点的磷酸化水平、总Tau蛋白水平和GSK-3β的蛋白表达水平均降低（P〈0．05）。在Rg1预处理组中，以20μmol／L Rg1预处理后Tau蛋白磷酸化水平、总Tau蛋白水平和GSK-3β的表达水平下降最为明显，而且PP2A的活性明显增强（P〈0．01）。结论人参皂苷Rg1可通过上调PP2A活性和下调GSK-3β活性从而减轻凝聚态Aβ25-35所诱导的皮层神经元Tau蛋白过度磷酸化。

英文摘要：

Objective To explore whether ginsenoside Rgl can attenuate β-amyloid peptide 25-35-induced Tan hyperphosporylation in rat embryo cortical neurons by regulating the activity of GSK-3β and PP2A. Methods Primary cultures of cortical neurons were prepared from the embryonic day 18 ± 2 in Sprague-Dawley rats. The experimental groups were designed as follows： 1. Neurons culture （control group）; 2. Neurons exposed to 20μmol/L Aβ25-35 for 12 hours （Aβ-model group）; 3. Neurons exposed to 20μmol/L Aβ25-35 and 10 mmol/L lithium chloride （LiCl）, a specific inhibitor of glycogen synthase kinase-3β（GSK-3β）, for 12 hours （LiCl group）; 4.Neurons exposed to 20μmol/L Aβ25-35 for 12 hours in the presence of 24-hour pretreatment with ginsenoside Rgl （Rgl pretreatment group） . Western blotting and immunocytochemical staining were used to detect the levels of Tan phosphorylation,total Tau and GSK-3β in cortical neurons. Non-radioimmunoassay was introduced to detect the activity of protein phosphatase 2A （PP2A）. Results In Aβ-model group, the levels of Tan protein phosphorylation in the sites of Ser^396 , Ser^199/202 ,Thr^231 and total Tau were enhanced. Meanwhile, the expression of GSK-3β was also increased, but the activity of PP2A was unchanged. In LiCl group and Rgl pretreatment group , the hyperposphorylations of Tan protein and total Tan and the expression of GSK-3β were markedly reduced compared to those of the Aβ-model group （P 〈 0.05）. 20μmol/L Rg1 pretreatment showed the best protective effect on attenuating Aβ25-35-induced Tau protein hyperposphorylation and the activity of GSK-3β, and markedly activated the activity of PP2A （ P 〈 0.01 ）. Conclusion Ginsenoside Rgl can attenuate Rg1-amyloid peptide 25-35-induced Tau hyperphosporylation in cortical neurons by inhibiting the activity of GSK-3β and activating the activity of PP2A.