秦皮乙素对Aβ_(25-35)诱导的Tau蛋白过度磷酸化的作用  

The effect of esculetin on Aβ_(25-35)-induced Tau hyperphosporylation

作　　者：梁珊珊[1] 陈汝筑[1] 朱小南[1] 曹舒雯[1] 汪雪兰[1] 

机构地区：[1]中山大学中山医学院药理教研室,广东广州510080

出　　处：《热带医学杂志》2013年第10期1181-1184,1213,共5页Journal of Tropical Medicine

基　　金：美国中华医学基金会CMB资助项目(98-677)

摘　　要：目的用Aβ25-35诱导HEK293细胞的Tau蛋白过度磷酸化建立Tau蛋白过度磷酸化的模型,探讨秦皮乙素(Esc)对该模型的作用及可能机制。方法采用不同浓度的Esc预孵HEK293细胞24 h,再用Aβ25-35诱导Tau蛋白过度磷酸化,Western blot检测Tau蛋白Ser396、Ser199位点磷酸化水平及GSK-3β磷酸化水平,以评价Esc对Aβ25-35诱导Tau蛋白过度磷酸化的影响及可能的作用机制。结果 10μmol/L Aβ25-35作用于HEK293细胞6 h,Tau蛋白Ser396和Ser199位点磷酸化水平分别是正常对照组的2.1和2.0倍,GSK-3β磷酸化水平增加至对照组的1.4倍,而预孵Esc(50、100、200μmol/L)24 h均可降低上述3个指标,其中200μmol/L作用最强,可使上述指标分别降低(57.2±5.3)%、(53.4±3.0)%和(59.3±2.1)%,与模型组比较差异均有统计学意义(P<0.05)。预孵10 mmol/L LiCl可使上述指标分别降低(39.4±5.6)%、(36.7±2.8)%和(39.6±2.6)%,与模型组比较差异有统计学意义(P<0.05)。结论Esc可降低Aβ25-35诱导的HEK293细胞Tau蛋白Ser396和Ser199位点过度磷酸化,该作用可能与Esc抑制GSK-3β活性有关。Objective To investigate the effects and mechanism of esculetin （Esc） on tau hyperphosporylation induced by Aβ25-35 Methods HEK293 cells were treated with Esc and then exposed to Aβ25-35. Western blot was applied to determine the expression of p-Tau（s396）, p-Tau（s199）, p-GSK-β（Y216）, Tau and GSK-313. Results The levels of Tau phosphorylation at the sites of Ser396 and Ser199 reached the maximum value（about 2 times as control group） after 6 hours exposure to A[3zs35. 50,100 and 200 μmol/L of Esc treatment can markedly reduced Aβ25-35-induced hyperphosphorylation of Tau. The best inhibitory effect was observed at 200 μmol/L of Esc which makes the p-Tau（s396）, p-Tau（s199） and p-GSK-3β（Y216） reduced by （57.2±5.3）%, （53.4±3.0）% and （59.3±2.1）%, respectively（P〈0.05）. 10 mmol/L LiCl made p-Tau（s396）, p-Tau（s199） and p-GSK-3β（Y216） reduced by （39.4±5.6）%, （36.7±2.8）% and （39.6±2.6）%, respectively （P〈0.05）. Conclusions Esc could attenuate the Aβ25-35-induced hyperphosporylation of Tau at the sites of Ser396 and Ser199. This effect may be related with the inhibition of GSK-3β. These results suggest a potential therapeutic value for Esc in phosphorylation of Tau related diseases.

关 键 词：秦皮乙素 Β-淀粉样蛋白 磷酸化TAU蛋白 

分 类 号：R971[医药卫生—药品]