急性呼吸窘迫综合症大鼠肺组织全基因组DNA甲基化的探索研究

发布时间：2018-03-04 15:36

本文选题：脂多糖　切入点：急性肺损伤　出处：《滨州医学院》2013年硕士论文　论文类型：学位论文

【摘要】：[目的]探讨LPS诱导的大鼠ARDS中肺组织全基因组DNA甲基化的变化,为进一步阐明ARDS的发病机制提供实验依据。 [方法]成年健康雄性SD大鼠12只,随机分为正常对照组(control组)、ARDS模型组(LPS组),于12h处死,行动脉血气分析,肺干湿重比值,肺组织HE染色及病理学观察,罗氏甲基化芯片检测肺组织全基因组DNA甲基化改变。 [结果]1、血气分析结果示：与Control组比较,PaO2在LPS组术后12h,明显下降(P0.05),PaO2/FiO2200mmHg；2、肺干湿重比值结果示：与Control组比较,LPS组术后12h肺干湿重比值明显升高(P0.05)；3、肺组织病理学结果示：LPS组术后12h,肺泡壁增厚,肺泡及间质水肿充血,间质中性粒细胞浸润及部分肺组织完全实变。4、两组对比,启动子区1721个基因和CpG岛中990个基因发生甲基化改变。5、甲基化基因分布在所有染色体上,但染色体1、3、5、7和10上基因数目有明显差异(P0.01)。6、分析CG含量的高(HCP)、中(ICP)和低(LCP)密度区,HCP区基因变化明显(P0.01)。7、GO注释筛选出14个已被证明与LPS诱导的ALI／ARDS有关的甲基化基因。8.KEGG通路分析筛选出10个基因富集的信号通路。 [结论]在LPS诱导的大鼠ALI／ARDS肺组织中,存在DNA甲基化的变化,这些异常DNA甲基化的变化在ALI／ARDS的病理生理过程中起到重要作用,这可能会成为ALI／ARDS有价值的预后标志物,并构成未来治疗的新靶点。
[Abstract]:[objective] to investigate the changes of genomic DNA methylation of lung tissue in rat ARDS induced by LPS, and to provide experimental evidence for further elucidating the pathogenesis of ARDS. [methods] Twelve adult male Sprague-Dawley rats were randomly divided into two groups: control group (n = 12) and LPS group (n = 12). Arterial blood gas analysis, lung dry / wet weight ratio, lung HE staining and pathological observation were performed. The genomic DNA methylation of lung tissue was detected by Roche methylation chip. [results] 1. The results of blood gas analysis showed that compared with Control group, PaO2 significantly decreased P0.05 / FiO2200mmHg2 in LPS group, and lung dry-wet weight ratio significantly increased P0.053in Control group 12 hours after operation. The alveolar wall thickened at 12 hours after operation. Pulmonary alveolar and interstitial edema, interstitial neutrophil infiltration and complete consolidation of some lung tissues were observed in two groups. The methylation changes occurred in 1721 genes in promoter region and 990 genes in CpG island. The methylation genes were distributed on all chromosomes. However, there were significant differences in the number of genes on chromosome 1, 3, 3, 5, 5, 7 and 10. There were significant differences in the number of genes on chromosome 1, 3, 5, 5, 7. 6. By analyzing the changes of genes in the high, middle and low density regions of CG, 14 methylated genes, which have been proved to be related to ALI/ARDS induced by LPS, have been screened out. A total of 10 gene-enriched signaling pathways were screened by path analysis. [conclusion] there are DNA methylation changes in the lung tissue of ALI/ARDS rats induced by LPS. These abnormal DNA methylation changes play an important role in the pathophysiological process of ALI/ARDS, which may be a valuable prognostic marker for ALI/ARDS. And constitute a new target for future treatment.
【学位授予单位】：滨州医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R563.8

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