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神经退行性疾病的发生过程中,引起神经细胞失活和凋亡的因素有很多,其中有研究显示,细胞周期因子被激活后,会导致神经元的异常反应甚至细胞凋亡。为此,我们用小鼠和PC12细胞建立急性和慢性乙醇诱导神经细胞凋亡的模型,研究细胞周期因子在神经细胞凋亡中的作用。然后,我们在急性乙醇刺激PC12细胞模型上,使用p53抑制剂和CDK4抑制剂来探究p53,cyclin D1和CDK4在caspase-3通路介导的凋亡中的作用。结果表明,一次给予大剂量乙醇会引发小鼠神经元内的p53,CDK4和cyclin D1的高表达和细胞凋亡,而长期低剂量的乙醇对小鼠神经细胞凋亡的作用并不明显。进一步研究显示,p53抑制剂能够降低caspase-3对乙醇刺激的响应,降低PC12细胞凋亡,然而CDK4抑制剂并不具有类似效果。阻断p53/caspase-3通路可以为乙醇代谢、以及细胞自身修复乙醇所致损伤赢得时间。总之,乙醇诱导的神经细胞凋亡与p53/caspase-3通路的激活有关,阻断p53的功能能够防治神经细胞损伤。
There are many factors that cause the inactivation and apoptosis of nerve cells during the development of neurodegenerative diseases. Some studies have shown that the activation of the cell cycle factor leads to the abnormal response of neurons and even apoptosis. To this end, we established acute and chronic ethanol-induced neuronal apoptosis models using mouse and PC12 cells to study the role of cell cycle factors in neuronal apoptosis. We then explored the role of p53, cyclin D1 and CDK4 in caspase-3 pathway-mediated apoptosis using a p53 inhibitor and a CDK4 inhibitor on acute ethanol-stimulated PC12 cell models. The results showed that high dose of ethanol could induce the high expression of p53, CDK4 and cyclin D1 in mouse neurons, while the effect of long-term low dose of ethanol on neuronal apoptosis was not obvious. Further studies showed that p53 inhibitors decreased the response of caspase-3 to ethanol stimulation and decreased the apoptosis of PC12 cells. However, CDK4 inhibitors did not have similar effect. Blocking the p53 / caspase-3 pathway can result in ethanol metabolism as well as the time it takes for cells to repair their own damage caused by ethanol. In conclusion, ethanol-induced neuronal apoptosis is associated with the activation of the p53 / caspase-3 pathway, blocking p53 function to prevent nerve cell injury.