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目的观察STZ诱导的糖尿病模型小鼠心肌组织中microRNA(miRNA)的表达,对差异miRNA靶基因进行预测,为糖尿病心肌病的干预提供可选择的miRNA。方法建立T1DM小鼠模型,成模6周末,小鼠处死后留取并制备心肌组织标本用于形态学及分子生物学分析。采用RT2 miRNA PCR Arrays筛选差异表达的miRNA,并对差异miRNA靶基因进行生物信息学分析。结果成模6周末,组织学观察发现,模型组心肌细胞肥大明显,心肌肥大细胞分子标记B型尿钠肽(BNP)升高,组蛋白去乙酰化酶(Hdac1)降低(P<0.05)。基因芯片检测发现,模型组心肌组织中有13个差异表达的miRNA,其中miR-19a、miR-19b、miR-22、miR-503和miR-467e表达上调,miR-1、miR-29a、miR-30a、miR-96、miR-101a、miR-142-3p、miR-199-5p和miR-374表达下调。生物信息学分析发现,差异miRNA调控的靶基因与细胞增殖、凋亡、糖代谢和血管生成等生物学功能相关。结论 STZ诱导的糖尿病模型小鼠心肌组织miRNA表达谱发生改变,提示miRNA可能参与糖尿病心肌损伤过程。
Objective To observe the expression of microRNA (miRNA) in myocardium of STZ-induced diabetic mice and to predict the target genes of differentially expressed miRNAs, so as to provide alternative miRNAs for the intervention of diabetic cardiomyopathy. Methods The T1DM mouse model was established. At the end of 6 weeks, the mice were sacrificed, and the myocardial tissue samples were collected for morphological and molecular biological analysis. The differentially expressed miRNAs were screened by RT2 miRNA PCR Arrays, and the bioinformatics analysis of differential miRNA target genes was performed. Results Six weeks after operation, histological examination showed that myocardial cell hypertrophy was markedly observed in model group, while BNP and Hdac1 were decreased in model group (P <0.05). Gene microarray assay showed that 13 differentially expressed miRNAs were found in myocardial tissue of model group. The expression of miR-19a, miR-19b, miR-22, miR-503 and miR-467e were up- -30a, miR-96, miR-101a, miR-142-3p, miR-199-5p and miR-374. Bioinformatics analysis showed that the target genes regulated by miRNAs were related to biological functions such as cell proliferation, apoptosis, glucose metabolism and angiogenesis. Conclusion The expression of miRNA in myocardial tissue of STZ-induced diabetic mice changes, suggesting that miRNA may be involved in the process of myocardial injury.