Genome-wide Analysis Of DNA Methylation In Rat Lung With Acute Respiratory Distress Syndrome

[Objective] To investigate the alteration of genome-wide DNA methylation by LPS induced ARDS in rat lung,and provide the experimental basis of further clarifing the pathogenesis of ARDS.[Metheds] Twelecve male rats divided into two groups randomly:Control group and ARDS model group (LPS group),the animals were killed12h after surgery, and then arterial blood gas.. lung wet/dry weight ratio and pulmonary histopathology were measured.Then genome-wide DNA methylation were observed by Roche-NimbleGen Rat DNA methylation microarray.[Results]1、Blood gas showed that compared with Control group, PaO2in LPS group was significantly decreased (P<0.05), PaO2/FiO2<200mmHg;2、The results of lung wet/dry weight ratio showed animals in LPS group had increased lung wet/dry weight rtio (P<0.05);3、Lung tissue pathology indicated the thickening of alveolar walls、 alveolar and interstitial edema hyperemia、interstitial infiltration by neutrophils and part of lung tissue completely consolidation;4、1721genes in promoter and990genes in CpG island were significantly aberrant DNA methylated compared normal with lung tissues by LPS-induced;5、The candidate genes were distributed across all chromosomes and these genes were located particularly on chromosomes1,3,5,7, and10(P<0.01);6、DNA methylation has a higher incidence on HCP genes compared to ICP and LCP genes (P<0.01);7、We selected14methylaed genes form GO term resluts which were association studies with positive findings in ALI/ARDS;8、The top10significant enrichment pathways were selected according to KEGG pathway analysis.[Conclusions] DNA methylation are involved in the lung tissues with LPS-induced ALI/ARDS in rat, and aberrant DNA methylation plays an important role in the pathophysiology of ALI/ARDS, which might be of value as prognostic biomarkers and constitute future therapeutic targets.