达格列净保护PDK1基因敲除心衰小鼠表达谱系研究
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南京医科大学科技发展基金(NMUB2018157)


LncRNA expression profiling induced by dapagliflozin in mice with heart failure
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    摘要:

    探讨钠-葡萄糖协同转运蛋白 2(SGLT2)抑制剂达格列净(DAPA)对3-磷酸肌醇依赖性蛋白激酶-1(PDK1)基因敲除心力衰竭(HF)小鼠中长链非编码RNA(lncRNA)表达谱的影响。方法 将PDK1敲除HF小鼠分为对照组(KO组,n=10)和达格列净治疗组(KO+DAPA组,n=15);使用Arraystar小鼠lncRNA微阵列通过测序和筛选分析lncRNA表达谱;实时定量PCR验证差异表达的LncRNA;构建lncRNA-mRNA共表达网络。结果 KO+DAPA组显著延长HF小鼠生存期;两组表达水平变化>1.5倍lncRNAs有2653个;生信分析表明lncRNAs参与能量代谢过程;差异表达大于3倍以上且人鼠同源的7个LncRNAs构建lncRNA-mRNA共表达网络提示uc.347和uc.321分别关联141个mRNA和108个mRNA;uc.347 在心肌细胞中的过表达促进了ATP能量的产生。结论 本研究揭示了达格列净影响PDK1基因敲除心衰小鼠lncRNA表达谱,差异表达的LncRNA可能参与能量代谢过程,从而改善心衰预后

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    To investigate the effect of SGLT2 inhibitor on lncRNA expression profiles in PDK1 knockout mice with heart failure. Methods PDK1 knockout mice were divided into control group and dapagliflozin(DAPA) treatment group. Arraystar mouse lncRNA microarray was used to analyze lncRNA expression profile by sequencing and screening. The real-time quantitative PCR was used to verify differentially expressed LncRNA. The lncRNA- mRNA co-expression network. Results KO+DAPAgroup significantly prolonged the survival of heart failure mice. There were 2653 lncRNAs in the two groups whose expression levels changed >1.5 times; bioinformatics analysis showed that lncRNAs were involved in energy metabolism. The differential expression was greater than 3 times and the above-mentioned 7 LncRNAs homologous to human and mouse construct a lncRNA-mRNA co-expression network, suggesting that uc.347 and uc.321 are associated with 141 mRNAs and 108 mRNAs, respectively. The overexpression of uc.347 in cardiomyocytes promotes the production of ATP energy. Conclusion This study revealed that dapagliflozin affects the lncRNA expression profile of PDK1 knockout mice with heart failure, and the differentially expressed lncRNA may be involved in the process of energy metabolism, thereby improving the prognosis of heart failure

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  • 在线发布日期: 2023-03-17
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