Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, west 16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
Int J Mol Sci. 2019 Apr 1;20(7):1614. doi: 10.3390/ijms20071614.
Dexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, directly protects hearts against ischemia/reperfusion (I/R) injury. However, the detailed mechanism has not been fully elucidated. We studied differentially expressed mRNAs and miRNAs after DEX administration in rat hearts by comprehensive analysis. Additionally, bioinformatics analysis was applied to explore candidate genes and pathways that might play important roles in DEX-induced cardioprotection. The results of microarray analysis showed that 165 mRNAs and 6 miRNAs were differentially expressed after DEX administration. Through bioinformatics analysis using differentially expressed mRNAs, gene ontology (GO) terms including MAP kinase tyrosine/serine/threonine phosphatase activity and pathways including the p53 pathway were significantly enriched in the down-regulated mRNAs. and were associated with the GO term of MAP kinase tyrosine/serine/threonine phosphatase activity and the p53 pathway, respectively. On the other hand, no significant pathway was found in the target mRNAs of deregulated miRNAs. The results indicated some possible key genes and pathways that seem to be of significance in DEX-induced cardioprotection, although miRNAs seem to be unlikely to contribute to cardioprotection induced by DEX.
右美托咪定（DEX）是一种高选择性的α2肾上腺素能受体激动剂，可直接保护心脏免受缺血/再灌注（I/R）损伤。然而，其详细机制尚未完全阐明。我们通过综合分析研究了 DEX 给药后大鼠心脏中差异表达的 mRNAs 和 miRNAs。此外，还应用生物信息学分析探讨了可能在 DEX 诱导的心脏保护中发挥重要作用的候选基因和途径。微阵列分析的结果表明，DEX 给药后有 165 个 mRNAs 和 6 个 miRNAs 表达差异。通过使用差异表达 mRNAs 的生物信息学分析，GO 术语（包括 MAP 激酶酪氨酸/丝氨酸/苏氨酸磷酸酶活性）和途径（包括 p53 途径）在下调的 mRNAs 中显著富集。和分别与 MAP 激酶酪氨酸/丝氨酸/苏氨酸磷酸酶活性和 p53 途径的 GO 术语相关。另一方面，在失调 miRNA 的靶 mRNAs 中未发现显著的途径。结果表明，DEX 诱导的心脏保护中可能存在一些关键基因和途径，但 miRNA 似乎不太可能对 DEX 诱导的心脏保护起作用。
