本文選題：脂多糖　切入點(diǎn)：急性肺損傷　出處：《濱州醫(yī)學(xué)院》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：[目的]探討LPS誘導(dǎo)的大鼠ARDS中肺組織全基因組DNA甲基化的變化,為進(jìn)一步闡明ARDS的發(fā)病機(jī)制提供實驗依據(jù)。 [方法]成年健康雄性SD大鼠12只,隨機(jī)分為正常對照組(control組)、ARDS模型組(LPS組),于12h處死,行動脈血?dú)夥治?肺干濕重比值,肺組織HE染色及病理學(xué)觀察,羅氏甲基化芯片檢測肺組織全基因組DNA甲基化改變。 [結(jié)果]1、血?dú)夥治鼋Y(jié)果示：與Control組比較,PaO2在LPS組術(shù)后12h,明顯下降(P0.05),PaO2/FiO2200mmHg；2、肺干濕重比值結(jié)果示：與Control組比較,LPS組術(shù)后12h肺干濕重比值明顯升高(P0.05)；3、肺組織病理學(xué)結(jié)果示：LPS組術(shù)后12h,肺泡壁增厚,肺泡及間質(zhì)水腫充血,間質(zhì)中性粒細(xì)胞浸潤及部分肺組織完全實變。4、兩組對比,啟動子區(qū)1721個基因和CpG島中990個基因發(fā)生甲基化改變。5、甲基化基因分布在所有染色體上,但染色體1、3、5、7和10上基因數(shù)目有明顯差異(P0.01)。6、分析CG含量的高(HCP)、中(ICP)和低(LCP)密度區(qū),HCP區(qū)基因變化明顯(P0.01)。7、GO注釋篩選出14個已被證明與LPS誘導(dǎo)的ALI／ARDS有關(guān)的甲基化基因。8.KEGG通路分析篩選出10個基因富集的信號通路。 [結(jié)論]在LPS誘導(dǎo)的大鼠ALI／ARDS肺組織中,存在DNA甲基化的變化,這些異常DNA甲基化的變化在ALI／ARDS的病理生理過程中起到重要作用,這可能會成為ALI／ARDS有價值的預(yù)后標(biāo)志物,并構(gòu)成未來治療的新靶點(diǎn)。
[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.
【學(xué)位授予單位】：濱州醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R563.8

【共引文獻(xiàn)】

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本文編號：1566290