链脲佐菌素诱导的糖尿病小鼠心肌组织中microRNA的表达

The expression changes of microRNA in the heart of streptozotocin-induced diabetic mice

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 investigate the microRNA （miRNA） differential expression profiles of heart in streptozotocin-induced diabetic mice and to find the potential target genes. Methods C57BL/6 mice were injected in peritoneal with STZ to estabish T1DiVL At the end of six weeks, the mice were sacrificed, the whole heart were collected for further analysis. The morphology of heart was detected using HE staining, the miRNA expression profile was detected by using RT2 miRNA PCR Arrays. The array was analyzed by bioinformatics for predicting the target genes. Results At the end of six weeks, histological observation showed that heart hypertrophy and the hypertrophy biomarker BNP were significantly higher in model group than in control group, but Hdacl significantly lower （P^0. 05）. There were 13 miRNA differential expressions in model group detected by RTz miRNA PCR Arrays, including five up-regulated （miR-19a, miR-19b, miR-22, miR-503, miR-467e） and eight down-regulated （miR-1, miR-29a, miR-30a, miR-96, miR-101a, miR-142-3p, miR-199-5p, miR-374）. These miRNAs participate in the regulation of cell proliferation, apoptosis, glycometabolism, and angiogenesis by the bioinformatics analysis. Conclusion Profiles of miRNA expression and bioinformatics analysis suggest miRNA plays an important role in the process of diabetic cardiomyopathy in STZ-induced diabetic mice.