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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。
Objective To study the mechanism of DNA methylation and PP1γ gene expression in mice hypoxic preconditioning model with time after hypoxia, and to elucidate whether hypoxia can regulate PP1γ expression through DNA methylation and exert its neuroprotective effect. Methods Mice were injected intracerebroventricularly with 5-aza-cdR (10μM, 5μl), followed by hypoxia. Mice were sacrificed on days 0, 1, 2, 3 and 4 after hypoxia, respectively. Transforming enzymes DNMTs and PP1γ mRNA expression changes. Results The DNMT1 mRNA expression was inhibited at 1 day after hypoxia and at 2 days after hypoxia (P <0.05), and was not affected by the activity of methyltransferase. 5-aza-cdR had no effect on the expression of DNMT1 (P> 0.05), but significantly inhibited the expression of DNMT3A (P <0.05). Hypoxia inhibited PP1γmRNA expression (P <0.05), and there was a time-dependent manner after hypoxia. Methyltransferase inhibited the expression of PP1γ (P <0.05), and was related to the time after hypoxia. Conclusion Hypoxia modulates the expression of PP1γ gene by changing the DNA methylation, especially the expression of DNMTs, and accomplishing its neuroprotective effect.