Bisoprolol, a β1 antagonist, protects myocardial cells from ischemia-reperfusion injury via PI3K/AKT/GSK3β pathway
Bisoprolol, a β1 antagonist, protects myocardial cells from ischemia-reperfusion injury via PI3K/AKT/GSK3β pathway
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Bisoprolol 是一种 β 1 拮抗剂，通过 PI3K/AKT/GSK3β 途径保护心肌细胞免受缺血再灌注损伤
DOI：
10.1111/fcp.12562
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发表时间：
2020-05-25
影响因子：
2.9
通讯作者：
Gong, Jianbin
中科院分区：
文献类型：
--
作者：
Wang, Jing;Liu, Jing;Gong, Jianbin
本工作的目的是探讨比索洛尔是否通过 PI3K/AKT/GSK3 beta 通路对心肌细胞缺血再灌注损伤发挥保护作用。我们在 0.5 小时缺血/4 小时再灌注之前通过口服比索洛尔对雄性 Sprague Dawley (SD) 大鼠进行预处理。测量心肌梗塞面积以及 cTnI 和 CK-MB 的血清水平。在体外，对 H9c2 细胞进行缺氧和复氧处理，然后在存在和不存在 GSK3 β siRNA 的情况下测量细胞活力、细胞凋亡、ROS 产生、细胞计数、AKT、GSK3 β 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% 减少到治疗组的 31%（P < 0.05）。 cTnI和CK-MB水平分别从I/R组的286±7pg/mL和32.2±2ng/mL下降至治疗组的196±2pg/mL和19.6±0.9ng/mL(P<0.05)。在缺氧/复氧治疗中，比索洛尔还可以增加细胞活力，同时减少细胞凋亡和 ROS 产生。此外，比索洛尔增加了 AKT 和 GSK3 β 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/复氧引起的损伤。总之，比索洛尔通过 PI3K/AKT/GSK3 β 途径保护心肌免受缺血再灌注损伤。
The aim of this work was to explore whether bisoprolol plays a protective role in cardiomyocytes against ischemia-reperfusion injury via PI3K/AKT/ GSK3 beta 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, GSK3 beta, and p-38 in the presence and absence of GSK3 beta 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 GSK3 beta phosphorylation, an effect that was immediately eliminated by LY294002. GSK3 beta-specific siRNA experiment further confirmed that bisoprolol protected the myocardium against hypoxia/reoxygenation-induced injury via suppressing GSK3 beta activity. In conclusion, bisoprolol protected myocardium against ischemia-reperfusion injury via the PI3K/AKT/ GSK3 beta pathway.