The aim of this work was to explore whether bisoprolol plays a protective role in cardiomyocytes against ischemia–reperfusion injury via PI3K/AKT/ GSK3β pathway. We pretreated male Sprague Dawley (SD) rats with bisoprolol by oral administration prior to 0.5 h ischemia/4 h reperfusion. Myocardial infarct size and serum levels of cTnI and CK‐MB were measured. In vitro, H9c2 cells were treated with hypoxia and reoxygenation, followed by measurement of cell viability, apoptosis, ROS production, cytometry, activities of AKT, GSK3β, and p‐38 in the presence and absence of GSK3β siRNA. We found that bisoprolol reduced infarct size from 44% in I/R group to 31% in treated group (P < 0.05). The levels of cTnI and CK‐MB were decreased from 286 ± 7 pg/mL and 32.2 ± 2 ng/mL in I/R group to 196 ± 2 pg/mL and 19.6 ± 0.9 ng/mL in the treated group, respectively (P < 0.05). Bisoprolol also increased cell viability while decreased apoptosis and ROS production in the treatment of hypoxia/ reoxygenation. Furthermore, bisoprolol increased AKT and GSK3β phosphorylation, an effect that was immediately eliminated by LY294002. GSK3β‐specific siRNA experiment further confirmed that bisoprolol protected the myocardium against hypoxia/reoxygenation‐induced injury via suppressing GSK3β activity. In conclusion, bisoprolol protected myocardium against ischemia–reperfusion injury via the PI3K/AKT/ GSK3β pathway.

中文翻译：

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β1拮抗剂比索洛尔通过PI3K / AKT /GSK3β途径保护心肌细胞免受缺血再灌注损伤。

这项工作的目的是探讨比索洛尔是否通过PI3K / AKT /GSK3β途径在心肌细胞中发挥抗缺血-再灌注损伤的保护作用。我们在0.5小时局部缺血/ 4小时再灌注之前，通过比索洛尔对雄性Sprague Dawley（SD）大鼠进行了口服比索洛尔预处理。测量心肌梗塞面积和血清cTnI和CK‐MB水平。在体外，先对H9c2细胞进行缺氧和复氧处理，然后在存在和不存在GSK3βsiRNA的情况下测量细胞活力，凋亡，ROS产生，细胞计数，AKT，GSK3β和p-38的活性。我们发现比索洛尔将梗死面积从I / R组的44％降至治疗组的31％（P <0.05）。cTnI和CK-MB的水平分别从I / R组的286±7 pg / mL和32.2±2 ng / mL降至治疗组的196±2 pg / mL和19.6±0.9 ng / mL（P  <0.05）。在缺氧/复氧治疗中，比索洛尔还可以提高细胞活力，同时减少细胞凋亡和ROS的产生。此外，比索洛尔增加了AKT和GSK3β磷酸化，这一作用立即被LY294002消除。GSK3β特异性siRNA实验进一步证实，比索洛尔通过抑制GSK3β活性来保护心肌免受缺氧/复氧诱导的损伤。总之，比索洛尔通过PI3K / AKT /GSK3β途径保护心肌免受缺血/再灌注损伤。