BKCa通道介导的右美托咪定剂量依赖性的大鼠心脏保护作用背景方法.PDFVIP

BKCa 通道介导的右美托咪定剂量依赖性的大鼠心脏保护作用 The Cardioprotective Effect of Dexmedetomidine in Rats Is Dose-Dependent and Mediated by BKCa Channels. 摘要翻译： 田 磊 原文摘要： The alpha-2 receptor agonist Dexmedetomidine (Dex) protects the heart against ischemia- reperfusion injury. We investigated the signaling cascade underlying Dex-induced acute cardioprotection, with special emphasis on large-conductance Ca2+-sensitive potassium (BKCa) channels. Rats were anesthetized with pentobarbital. Hearts were isolated, mounted on a Langendorff system and perfused with Krebs-Henseleit buffer. Hearts underwent 33 minutes of ischemia followed by 60 minutes of reperfusion. Before the beginning of ischemia, Dex was administered at different doses (0.1-30 nM) for characterization of a dose-effect relationship. In another set of experiments, Dex (3 nM) was administered together with the BKCa channel inhibitor paxilline and the connexin-43 inhibitor peptide Gap27. Also, the BKCa channel opener NS1619 was administered. In control animals, infarct size was 49% ± 5%. Dex at 3-30 nM reduced infarct size to ∼22%, whereas lower (0.1-1 nM) doses reduced infarct size to ∼38%. Paxilline (1 μM) and GAP27 (6 μM) blocked the Dex-induced cardioprotection. NS1619 (10 μM) reduced infarct size to about the same magnitude as did the higher doses of Dex. Functional heart parameters and coronary flow were not different between the study groups. In male rats, the Dex-induced protection against ischemia-reperfusion injury involves connexin-43 and activation of BKCa channels. 中文摘要： 背景 α2受体激动剂右美托咪定(Dex)可保护心肌免受缺血-再灌注损伤。 我们研究了 Dex 诱导的急性心肌保护作用下的信号级联反应，并特别关注了大电导钙依赖钾离子 （BKCa）通道。 方法 戊巴比妥麻醉雄性大鼠后，分离心脏，安置在 langendorff 灌注系统上，并灌入 krebs-henseleit 缓冲液。心脏缺血 33 分钟，再灌注 60 分钟。在缺血开始之前， Dex以不同剂量（0.1-30nm）给药，用于描述药物的剂量-效应关系。另一组实验中， Dex （3nm）与BKCa 通道抑制剂蕈青霉素和缝隙连接蛋白 43 抑制剂 GAP27 联合应用。 另