Akt信号通路在非典型性抗精神病药物阿立哌唑调节海马神经细胞凋亡中的作用

发布时间：2018-04-25 15:39

  本文选题：阿立哌唑 + Akt信号通路　； 参考：《中国老年学杂志》2017年09期

【摘要】：目的探讨非典型性抗精神病药物阿立哌唑是否通过Akt信号通路对海马神经细胞的凋亡发挥作用。方法通过构建精神分裂症(CPZ)模型小鼠,设置对照组、阿立哌唑组、CPZ组、CPZ+阿立哌唑四组,实验结束后对小鼠断头取脑,冰上分离出海马组织和脊髓,培养海马神经细胞,流式细胞仪检测细胞凋亡情况,MTT检测细胞增殖、Western印迹检测自噬相关蛋白Beclin1的表达情况;使用磷酸化Akt信号通路试剂盒对总Akt,磷酸化Akt(Ser473)含量的变化情况进行检测。结果对饲养6 w后的小鼠提取海马神经细胞,流式细胞仪、MTT检测结果表明,建立CPZ模型的小鼠,在饲养过程中使用阿立哌唑能明显降低海马神经细胞的凋亡率;MTT检测结果表明,与对照组相比,使用阿立哌唑的CPZ模型小鼠海马神经细胞的存活率明显提高(P0.01);Western印迹检测自噬相关蛋白Beclin1的结果表明,构建的CPZ模型小鼠脊髓受到一定程度损伤,Beclin1的表达量明显升高(P0.01),给阿立哌唑后其表达量显著下降;在CPZ组中总Akt及Ser473的表达水平均显著下降(P0.01),通过服用阿立哌唑后表达水平出现回升,与对照组相比差异不显著(P0.05)。结论非典型性抗精神病药物阿立哌唑可通过Akt信号通路使海马神经细胞免于凋亡。
[Abstract]:Aim to investigate whether aripiprazole, an atypical antipsychotic drug, plays an important role in hippocampal neuronal apoptosis through Akt signaling pathway. Methods the model mice with schizophrenia (CPZ) were set up as control group and aripiprazole group (CPZ group) as CPZ group. After the experiment, hippocampus and spinal cord were isolated and hippocampal nerve cells were cultured. Apoptosis was detected by flow cytometry and the expression of autophagy associated protein (Beclin1) was detected by Western blotting, and the changes of total Akt, phosphorylated Aktfen Ser473 were detected by phosphorylated Akt signal pathway kit. Results the hippocampal neurons were extracted from the mice fed for 6 weeks. The results of flow cytometry showed that aripiprazole could significantly reduce the apoptosis rate of hippocampal neurons in CPZ model mice. Compared with the control group, the survival rate of hippocampal neurons in CPZ model mice treated with aripiprazole was significantly increased by Western blot analysis of autophagy associated protein Beclin1. The expression of Beclin1 in spinal cord of CPZ model mice was significantly increased after administration of aripiprazole, and the expression of Beclin1 was significantly decreased after administration of aripiprazole. The expression levels of total Akt and Ser473 in CPZ group were significantly lower than those in the control group (P 0.01). After taking aripiprazole, the expression level of total Akt and Ser473 increased, but there was no significant difference compared with the control group (P 0.05). Conclusion aripiprazole can protect hippocampal neurons from apoptosis through Akt signaling pathway.
【作者单位】： 武汉市精神卫生中心医务处;武汉市中医医院院办;武汉市精神卫生中心司法鉴定科;武汉市精神卫生中心综合科;
【基金】：湖南省自然科学基金(No.2015JJ1010)
【分类号】：R749.4
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本文编号：1801944