Objective To investigate the differential expression profiles of microRNAs in the liver of 60Co γ-ray irradiated mice using microRNA microarray and to explore their main functions by bioinformatic analysis.Methods After SPF C57BL/6J mice expose to 4 Gy-single whole body radiation,total number of peripheral WBC and the fMNPCE were measured at 3 d.The differentially expressed miRNAs in mouse liver were detected with miRNA microarray,miRNA-124 and miR-34a were confirmed by real time RT-PCR assay.Bioinformatic analysis was applied to explore target genes and the main functions of the differential expressed miRNAs.Results Compared with control group,the total number of peripheral WBC decreased( t = 2.87,P ＜ 0.05 ) ,while the fMNPCE in bone marrow increased ( t =-2.91,P ＜0.05) after 4 Gy γ-ray irradiation.miRNA microarray revealed that 17 miRNAs were differentially expressed,in which 9 up-regulated,8 down-regulated.The expression levels of miR-124 and miR-34a were coincident with the result of real time RT-PCR.GO analysis showed that some pathways including adherens junction and cell cycle were suppressed,while some immune-related pathways were activated.Conclusions miR-34a and miR-194 were involved in the regulation of acute radiation damage,some other miRNAs including miR-124、miR-382 and miR-92a* also played important roles in radiation process.

Objective To study the change and significance of DNA methylation pattern and DNA methyltransferase(DNMT1) protein in 60Co γ-ray irradiated mice tissues.Methods Twelve SPF C57BL/6J mice were randomly divided intocontrol group and radiation group.The radiation group were exposed to 4Gy-single whole body radiation.All mice were sacrificed 3 days after the radiation.The total number of peripheral white blood cells and the frequencies of micronucleated polychromatic erythocytes(fMNPCE) were measured.Methylated DNA immunoprecipitation-chip(MeDIP-chip) was adopted to investigate the differentially expressed CpG islands methylation profiles in mouse liver genome promoter.The immunohisto-chemical(SP method) and western blot method were used to check the expression of DNMT1 protein in tissues.Results Compared with the control group,the promoter methylation profiles of irradiated mice changed obviously,with 1300 genes methylated and 660 genes demethylated.With the improvement of the screening criteria,the obviously methylated genes were Trim71,Sema3f,Pcdh8,Sox4,1110034A24Rik,Limk1,Nefl,and Xpr1 and the demethylated genes were Sfrs18,Dr1,Ankrd42,Nae1,Sfi1,Accn1,Srd5a1,Nsun2,Eif1a,and Dusp5.Except in the lung,the expression of DNMT1 protein in liver,kidney,testicle,and brain tissues were all increased(P0.05).Conclusion There are methylation changes of gene promoter in ionizing radiation injury and the increased expression of DNMT1 may be the reason of gene promoter methylation.

研究[1,2]认为,一些复杂性疾病与DNA甲基化、基因组印记、X染色体失活以及非编码RNA调控等表观遗传过程相关.现将表观遗传学的基本机制和与表观遗传学相关的神经发育性疾病论述如下.

本文建立氚水染毒小鼠模型，采用甲基化DNA免疫沉淀-芯片(MeDIP-chip)杂交技术分析小鼠肝组织基因启动子CpG甲基化情况，并检测了肺、肝、肾脏组织DNMT1的表达水平。结果显示，不同浓度氚染毒10 d的小鼠肝脏组织基因组出现了新的甲基化位点，而且高浓度和低浓度染毒组的共同发生甲基化的基因有19个，17个发生在启动子的CpG。随着氚水初始注入量增加，累积剂量增大，肺、肝、肾组织DNMTl表达量相应降低。氚水初始注入量为5.55×105 Bq/g时，随注入后时间延长，累积剂量增大，DNMTl表达量下降后再恢复。实验结果提示，甲基化改变的差异基因可能在氚水内照射损伤时起调控作用，不同组织中DNMT1的检测可用于辐射损伤的早期检测或损伤恢复的评估。