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目的探讨帕潘立酮对地佐环平损伤大鼠脑皮层神经元的保护作用及机制。方法取孕15 d胎鼠脑皮层神经元体外培养,应用地佐环平损伤神经元,然后加入不同浓度的帕潘立酮。采用MTT技术检测脑皮层神经元的生长活性,采用酶标仪检测乳酸脱氢酶(LDH)的活性及激光共聚焦技术检测神经元细胞内Ca2+浓度观察神经元凋亡情况,通过神经元突起数目及长度检测神经元生长情况,应用实时定量PCR技术检测Akt1、GSK3β的表达变化。结果与正常对照组相比,地佐环平损伤组神经元活性明显下降,LDH释放增加,细胞内游离钙离子浓度升高(P均<0.01),神经元突起总长度下降,神经突起数目呈现不同程度的减少(P<0.01),RT-PCR结果显示,Akt1及GSK3β表达下降(P<0.01);加入不同浓度的帕潘立酮能明显对抗地佐环平对神经元的损伤,MTT结果显示神经元活性升高(P<0.01),LDH活性明显降低(P<0.001),细胞内游离Ca2+浓度显著下降(P<0.01),神经突起数目和长度增加(P<0.01),Akt1及GSK3β表达上升(P<0.01)。结论帕潘立酮对地佐环平损伤脑皮层神经元具有明显保护作用,可抑制细胞凋亡,并通过Akt1-GSK3β通路促进神经突起的生长。
Objective To investigate the protective effect and mechanism of paliperidone on cortical neurons in rats with daizocine. Methods Cortical neurons of fetus were cultured in vitro for 15 days. Neurons were induced by diltiazem and then added with different concentrations of paliperidone. The activity of neurons in cortical neurons was detected by MTT assay. The activity of lactate dehydrogenase (LDH) was measured by microplate reader and the concentration of Ca2 + in neurons was detected by laser scanning confocal microscope. The number of neurons And length of neurons were detected. Real-time quantitative PCR was used to detect the expression of Akt1 and GSK3β. Results Compared with the normal control group, the activity of neurons decreased significantly in the group of dezocepin-induced injury, the release of LDH increased, the concentration of intracellular free calcium increased (P <0.01), the total length of neurons decreased and the number of neurites appeared RT-PCR results showed that the expression of Akt1 and GSK3βdecreased (P <0.01); the addition of different concentrations of paliperidone significantly inhibited the neuronal damage of mitoxantrone, the MTT results (P <0.01), the activity of LDH decreased significantly (P <0.001), the concentration of free intracellular Ca2 + decreased significantly (P <0.01), and the number and length of neurites increased (P <0.01). The levels of Akt1 and GSK3β The expression increased (P <0.01). Conclusions Paliperidone can protect neurons from damaging the cerebral cortical neurons by daizepine, and can inhibit apoptosis and promote the growth of neurites through Akt1-GSK3β pathway.