当药醇苷对β淀粉样蛋白诱导神经细胞损伤模型GSK-3β及Akt表达的影响

The effect of swertianolin on the expressions of GSK-3 beta and Akt in nerve cell injury model induced by Aβ

目的研究当药醇苷对阿尔茨海默病(AD)细胞模型糖原合成酶激酶(GSK)-3β及蛋白激酶B(Akt)表达的影响及机制。方法10μmol/L Aβ作用于PC12细胞制作成AD细胞模型。实验分为正常对照组,模型组,当药醇苷低剂量组,当药醇苷高剂量组,LY294002组,LY294002+当药醇苷高剂量组。结果与正常对照组比较,模型组p-Akt蛋白水平明显下降(P<0.05),而p-GSK-3β蛋白显著升高(P<0.05)。与模型组比较,当药醇苷高、低剂量组p-Akt蛋白表达水平明显升高,p-GSK-3β蛋白表达显著下降(P<0.05);当药醇苷高、低剂量组间比较差异不显著(P>0.05);用LY294002处理的两组p-Akt蛋白和p-GSK-3β蛋白表达水平与正常对照组无显著差异(P>0.05),LY294002+当药醇苷高剂量组与当药醇苷高、低剂量组的p-Akt蛋白和p-GSK-3β蛋白表达水平比较有统计学差异(P<0.05)。结论当药醇苷可以拮抗Aβ导致的AD神经损伤,具有神经细胞保护作用,其作用机制可能通过激活PI3K/Akt信号通路,提高p-Akt蛋白表达水平,抑制该通路下游靶分子p-GSK-3β活性而实现。

Objective To explore the effect of Swertianolin against the Aβ-inducing PC12 cells（ Alzheimer＇s disease,AD） and evaluate the expression of glycogen synthase kinase（ GSK）-3β and protein kinase B（ Akt） after the treatment with Swertianolin to explore the mechanism involved in it.Methods AD model was induced by 10 μmol/L Aβ in PC12 cells. Cells were divided into： control,Aβ-inducing（ model）,low,high dose of Swertianolin,LY294002 inhibitor,LY294002 inhibitor ＋ high dose of Swertianolin groups.Results Compared with control group,the p-Akt protein level was significantly decreased（ P〈0.05）,while the p-GSK-3 protein was significantly increased（ P〈0.05） in model group. Compared with model group,p-Akt protein was significantly increased and p-GSK-3β protein was significantly decreased in high and low dose groups（ P〈0.05）. There were no significant differences in p-Akt and p-GSK-3β protein between high and the low dose groups（ P〉0.05）. There were no significant differences in expressions of p-Akt and p-GSK-3β protein among LY294002 inhibitor,LY294002 inhibitor ＋ high dose of Swertianolin groups and control group（ P〉0.05）. There were significant differences in expressions of pAkt and p-GSK-3β protein between LY294002 inhibitor ＋ high dose of Swertianolin and low,high dose of Swertianolin groups. Conclusions Swertianolin could reduce Aβ-inducing nerve injury in PC12 cell by increasing the expression of p-Akt protein and decreasing the activity of p-GSK-3βin the PI3 K/Akt signaling pathway.