心肌梗死小鼠不同时间点心肌组织mRNA表达谱的变化

Changes of mRNA expression profile of myocardial tissues in mice with myocardial infarction in different time periods

目的分析小鼠心肌梗死(MI)后7、14、28 d心肌组织mRNA表达谱的变化。方法将C57BL/6J小鼠随机分为假手术组(S组)和MI模型组(MI组),每组10只。采用结扎小鼠冠状动脉左前降支方法建立MI模型,行心电图和组织病理学检查验证,心脏彩超观察心脏结构变化。取梗死边缘区心肌组织进行转录组测序,筛选差异表达mRNA基因,采用基因本体(GO)分析和京都基因与基因组百科全书(KEGG)分析参与重要信号通路的差异表达基因。结果 MI组建模后3个时间点左心室舒张末期内径及其容积、左心室收缩末期内径及其容积均大于S组,而左心室射血分数低于S组(P<0.05)。MI组建模后3个时间点共280个基因均表达上调,而40个基因均表达下调。GO分析显示,持续表达上调或下调的基因主要参与的生物功能为生物调节、对刺激的反应、代谢过程、发育过程等;细胞成分有细胞膜、细胞核、囊泡、细胞外基质等;分子功能有蛋白结合、转运激活等。KEGG分析显示,持续表达上调的基因参与信号通路多促进心室重塑,持续表达下调的基因参与信号通路多抑制和延缓心室重塑。结论小鼠MI建模后心脏形态结构发生异常,心功能减低;不同时间点进行mRNA谱分析显示涉及基因数目众多且功能复杂。

Objective To analyze the changes of mRNA expression profile of myocardial tissue in mice on the 7th,14th and 28th day after myocardial infarction(MI).Methods C57 BL/6 J mice were randomly divided into sham operation group(group S) and MI model group(group MI) with 10 mice each.MI model was established by ligating the left anterior descending coronary artery.ECG and histopathological examinations were performed to verify the MI model.The myocardial structural changes were observed by echocardiography.Transcriptome sequencing of myocardial tissues was performed at the infarction margin,and differentially expressed mRNA genes were screened.Gene ontology(GO) analysis and Kyoto Gene and Genome Encyclopedia(KEGG) were used to analyze the differentially expressed genes involved in important signaling pathways.Results LVEDD,LVESD,LVEDV and LVESV in group MI were greater,but LVEF was lower in group MI than those in group S at 3 time points after MI(P<0.05).There were 280 up-regulated genes and 40 down-regulated genes in group MI at 3 time points after MI.GO analysis showed that the genes with continuous up-regulation or down-regulation were mainly involved in biological functions such as biological regulation,response to stimulation,metabolic process and development process.The cell components included membrane,nucleus,vesicle and extracellular matrix.The molecular functions included protein binding,transport activation and so on.KEGG analysis showed that the genes with continuously up-regulated expression were more involved in signaling pathways to promote ventricular remodeling,while the genes with continuously down-regulated expression were more involved in signaling pathways to inhibit or delay ventricular remodeling.Conclusion Cardiac morphologic structure is abnormal and cardiac function is decreased in the mice of MI model.The mRNA spectrum analysis at different time points may show that a large number of genes and their complex functions are involved.