Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.
Department of Pathology, Kunming Medical University, Kunming, Yunnan Province, China.
Biomed Pharmacother. 2020 May;125:110001. doi: 10.1016/j.biopha.2020.110001. Epub 2020 Feb 25.
Dexmedetomidine (Dex) has been reported to be cardioprotective. Differential expression of miR-208b-3p is associated with myocardial injury. But it is unknown that aberrant expression of miR-208b-3p is implicated in myocardial protection of Dex. Hypoxia/reoxygenation (HR) model was established in H9C2 cells. qRT-PCR was performed to detect expression levels of miR-208b-3p in H9C2 undergoing HR, Dex preconditioning, overexpression of miR-208b-3p or inhibition, and to assess expression of Med13 in H9C2 following knockdown of Med13 mRNA. CCK8 and, flow cytometry and Western blot were conducted respectively to examine viability, apoptosis rate and protein expressions of H9C2 subjected to a variety of treatments. Dex preconditioning reduced expression of miR-208b-3p and apoptosis of H9C2 cells caused by HR, while Dex preconditioning increased viability of H9C2. Dex preconditioning increased expression of Med13, which was reduced after knockdown of Med13 mRNA in H9C2. Overexpression of miR-208b-3p attenuated Dex exerted protective effects of myocardial cells, which was reversed by inhibition of miR-208b-3p. Increased expression of Med13 or/and decreased expression of miR-208b-3p decreased expression levels of Wnt/β-catenin signaling pathway-related proteins (Wnt3a, Wnt5a and β-catenin), while knockdown of Med13 mRNA or increased expression of miR-208b-3p increased the expression levels of those proteins. Dex protects H9C2 cells against HR injury through miR-208b-3p/Med13/Wnt/β-catenin signaling pathway axis.
右美托咪定（Dex）已被报道具有心脏保护作用。miR-208b-3p 的差异表达与心肌损伤有关。但是，miR-208b-3p 的异常表达是否与 Dex 的心肌保护作用有关尚不清楚。在 H9C2 细胞中建立缺氧/复氧（HR）模型。qRT-PCR 用于检测 HR、Dex 预处理、miR-208b-3p 过表达或抑制后 H9C2 中 miR-208b-3p 的表达水平，并评估 Med13 mRNA 敲低后 H9C2 中 Med13 的表达。CCK8 法、流式细胞术和 Western blot 分别用于检测各种处理后 H9C2 的活力、凋亡率和蛋白表达。Dex 预处理可降低 HR 引起的 H9C2 细胞中 miR-208b-3p 的表达和凋亡，同时增加 H9C2 的活力。Dex 预处理可增加 Med13 的表达，而 Med13 mRNA 敲低后 H9C2 中的 Med13 表达减少。miR-208b-3p 的过表达减弱了 Dex 对心肌细胞的保护作用，而 miR-208b-3p 的抑制则逆转了这种作用。Med13 表达增加和/或 miR-208b-3p 表达减少可降低 Wnt/β-catenin 信号通路相关蛋白（Wnt3a、Wnt5a 和 β-catenin）的表达水平，而 Med13 mRNA 敲低或 miR-208b-3p 表达增加可增加这些蛋白的表达水平。Dex 通过 miR-208b-3p/Med13/Wnt/β-catenin 信号通路轴保护 H9C2 细胞免受 HR 损伤。
