【摘要】 目的研究小鼠低氧预适应模型中DNA甲基化和PP1γ基因表达伴随低氧后时间的变化机制,阐明低氧是否通过DNA甲基化来调控PP1γ表达,发挥其脑保护作用。方法小鼠侧脑室注射5-aza-cdR(10μM,5μl),之后进行低氧处理,分别于低氧后0、1、2、3、4天处死小鼠,利用实时荧光定量PCR检测甲基转移酶DNMTs和PP1γmRNA的表达变化。结果低氧后1天DNMT1和低氧后2天DNMT3A的mRNA表达受到抑制(P<0.05),且不受甲基转移酶活性的影响。5-aza-cdR对DNMT1的表达没有影响(P>0.05);但明显抑制DNMT3A的表达(P<0.05)。低氧抑制PP1γmRNA表达(P<0.05),且有低氧后时间依赖性。甲基转移酶对PP1γ表达有抑制作用(P<0.05),且与低氧后时间有关。结论随着低氧后时间的延长,低氧通过改变DNA甲基化,尤其是DNMTs表达变化,调控PP1γ基因表达,实现其脑保护作用。更多还原

【Abstract】 Objective:In hypoxic preconditioned mouse model,to study the changes of DNA methylation and protein phosphatase 1 expressions with the time after hypoxia.To reveal the hypoxia may regulate the PP1γ expression via the DNA methylation to play role in brain neuroprotection.Methods:The experimental group mice were injected with 5-aza-cdR(10μmol/L,5 μl),then they were treated by hypoxia and last they were euthanasia after zero/one/two/three/four day’s hypoxia.Real-time PCR was used to examine the mRNA levels of DNMTs and PP1γ in the mice hippocampus.Results:The results showed that the mRNA level of DNMT1 was decreased after one day since hypoxia and DNMT3 A decreased after two day since hypoxia(P<0.05),those changes might not be affected by the activity of DNA methyltransferases.The mRNA level of DNMT3 B was restrained by 5-aza-cdR(P<0.05),but not DNMT1(P>0.05).The mRNA levels of PP1γ were down-regulated by hypoxia(P<0.05).The mRNA levels of PP1γ were increased with 5-aza-cdR(P<0.05),and the increases had the relationship with the time after hypoxia.Conclusion:As the extension of time after hypoxia,the hypoxia may regulate the expression of PP1γ via the change in DNA methylation,especially DNMTs expression,to take part in the brain neuroprotection.更多还原