阿魏酸钠通过Notch1/Hes信号通路对抗Aβ_(1-42)引起的SD胎鼠海马神经元凋亡

Sodium ferulate antagonizes apoptosis of hippocampal neurons induced by Aβ_(1-42) via Notch1/Hes signaling pathway in embryonic mice

目的 探讨阿魏酸钠(Sodium ferulate, SF)对Aβ_(1-42)引起的SD胎鼠海马神经元凋亡的抑制作用及相关机制。方法 原代培养海马神经元,选取培养8 d的成熟细胞,分为以下四组:对照组(Control,加入0.1%DMSO作用72 h);Aβ_(1-42)组(加入终浓度50 nmol/LAβ_(1-42)作用72 h);SF+Aβ_(1-42)组(先加入200μmol/LSF作用6h后再加入Aβ_(1-42));SF+Aβ_(1-42)+Jagged1组(Jagged1为Notch1/Hes信号通路激动剂,先加入200μmol/LSF和400μg/L Jagged1作用6 h后再加入Aβ_(1-42))。MTT检测细胞活力,TUNEL染色及流式细胞仪检测细胞凋亡情况,Western blot检测各组细胞Notch1、Hes、Bax及Bcl-2蛋白相对表达。结果 与Control组相比,Aβ_(1-42)组和SF+Aβ_(1-42)+Jagged1组海马神经元细胞活力明显降低,细胞凋亡率明显增加,Notch1、Hes及Bax蛋白表达水平明显增加,Bcl-2蛋白表达水平明显降低。而与Aβ_(1-42)组相比,SF+Aβ_(1-42)组细胞活力明显增加,细胞凋亡率明显降低,Notch1、Hes及Bax蛋白表达明显降低,Bcl-2蛋白表达明显增加。结论 SF对Aβ_(1-42)诱导的海马神经细胞凋亡具有明显的抑制作用,其机制与抑制Notch1/Hes信号通路的激活有关。

Objective To investigate the inhibitory effect of sodium ferulate(SF) on apoptosis of hippocampal neurons induced by Aβ_(1-42)1-4 2. Methods The primary cultured hippocampal neurons were divided into: control group(0.1%DMSO for 72 h), Aβ_(1-42)group(Aβ_(1-42), 50 nmol/L for 72 h), SF+Aβ_(1-42)group(200μmol/L SF for 6 h before Aβ_(1-42)),SF+Aβ_(1-42)+Jagged1 group(Jagged1 is a Notch1/Hes signal pathway activator, 200μmol/L SF) and 400μg/L Jagged 1 for 6hours before Aβ_(1-42)). MTT was used to detect cell viability, TUNEL staining and flow cytometry to detect apoptosis. The expressions of Notch1, Hes, Bax and Bcl-2 proteins were determined by Western blot. Results Compared with the control group, the activity of hippocampal neurons in the Aβ_(1-42)group and SF+Aβ_(1-42)+Jagged1 group was decreased significantly,the apoptosis rate was increased significantly, the expression levels of Notch1 and Hes and Bax proteins was increased, and the expression level of Bcl-2 protein was decreased significantly. Compared with Aβ_(1-42)group, cell viability was increased,the apoptosis rate was decreased significantly, the expression levels of Notch1 and Hes and Bax proteins was decreased significantly, but Bcl-2 protein expression was increased in SF+Aβ_(1-42)group. Conclusion SF inhibits the apoptosis of hippocampal neurons induced by Aβ_(1-42), which is related to the inhibition of Notch1/Hes signaling pathway.