摘要
目的:观察人参皂苷Rg1对阿尔茨海默病(Alzhei mer's disease,AD)样tau蛋白磷酸化大鼠脑片模型中磷酸化tau蛋白(phosphorylatedtau protein,P-tau)、蛋白磷酸酶2A(protein phosphatase 2A,PP2A)及tau蛋白表达的影响,以研究其对tau蛋白磷酸化的抑制作用机制。方法:将5周龄雄性Wistar大鼠脑片(含皮层和海马)随机分为空白对照组、模型组和低、中、高浓度人参皂苷Rg1组,每组10张脑片。脑片置于人工脑脊液中培养。人参皂苷Rg1组培养液中首先加入人参皂苷Rg1使其浓度分别为60、120和240μmol/L,作用2h。模型组和3个浓度人参皂苷Rg1组培养液中分别加入冈田酸(okadaic acid,OA),使其浓度分别为1μmol/L,作用3h,空白对照组不加任何处理。采用免疫组织化学染色、图像分析技术等方法,检测皮层和海马P-tau、PP2A和tau蛋白的表达水平。结果:与空白对照组比较,模型组P-tau蛋白的表达增加(P<0.01),PP2A和tau蛋白的表达水平降低(P<0.01,P<0.05);3个浓度人参皂苷Rg1组与模型组比较,P-tau蛋白的表达减少(P<0.01),PP2A和tau蛋白的表达增加(P<0.01,P<0.05),其中以高浓度人参皂苷Rg1效果最佳。结论:人参皂苷Rg1可以上调AD样tau蛋白磷酸化大鼠脑片模型中PP2A的表达从而促进P-tau的去磷酸化,以此途径抑制tau蛋白磷酸化。
Objective：To investigate the effects of gensenoside Rg1 on expressions of phosphorylated tau protein （P-tau）,protein phosphatase 2A （PP2A） and tau protein in Alzheimer＇s disease-like tau phosphorylation rat brain slices,and to explore the mechanisms of gensenoside Rg1 in inhibiting tau phosphorylation.Methods：Brains of 5-week-old Wistar rats were cut into slices which were 400 μm thick.These brain slices were randomly divided into blank control group,untreated group,low-dose ginsenoside Rg1 group,medium-dose ginsenoside Rg1 group and high-dose ginsenoside Rg1 group,with 10 slices in each group.All brain slices were cultured with artificial cerebrospinal fluid （ACSF）.And brain slices in the ginsenoside R1 groups were administered with ginsenoside Rg1 （60,120 and 240 μmol/L respectively） in ACSF for 2 h firstly.After 2-hour culture,okadaic acid （OA） was administered into ACSF of the untreated group and the ginsenoside Rg1 groups separately for 3 h to induce tau phosphorylation to prepare AD models.The concentration of OA in each group was 1 μmol/L.There was no any intervention for the brain slices in the blank control group.Expressions of P-tau,PP2A and tau proteins in the brain slices were determined by immunohistochemical method,and the results were analyzed by image acquisition and analysis system.Results：Compared with the blank control group,the expression of P-tau protein was significantly increased （P0.01） and the expressions of tau and PP2A proteins were decreased （P0.01,P0.05） in the untreated group.Compared with the untreated group,the expression of P-tau was significantly decreased （P0.01） and the expressions of tau and PP2A proteins were increased （P0.01,P0.05） in the ginsenoside Rg1 groups,especially in the high-dose ginsenoside Rg1 group.Conclusion：Ginsenoside Rg1 can promote dephosphorylation of P-tau by increasing the expression of PP2A in Alzheimer＇s disease-like tau phosphorylation rat brain slices,so as to inhibit tau phosphorylation.
出处
《中西医结合学报》
CAS
2010年第10期955-960,共6页
Journal of Chinese Integrative Medicine
基金
陕西省科技攻关计划项目[No:2007K16-07(5)]
陕西省中医药管理局基金项目(No:2002030)
