Abstract

Myocardial ischemia/reperfusion (I/R) injury has been found to be associated with oxidative stress. Plantamajoside (PMS) is a major compound of Plantago asiatica that was reported to possess cardioprotective and antioxidant effects. The current study was designed to investigate the effect of PMS on myocardial I/R injury. Rat cardiomyocytes H9c2 cells were exposed to hypoxia/reoxygenation (H/R) to establish in vitro model of myocardial I/R injury. MTT assay proved that H9c2 cells viability was significant reduced under H/R treatment, while the reduction was ameliorated by PMS. H/R-induced ROS production in H9c2 cells was suppressed by PMS. The decreased activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the H/R group were effectively elevated by PMS. In addition, treatment with PMS attenuated H/R-stimulated production of TNF-α, IL-6 and IL-1β in H9c2 cells. Besides, PMS significantly suppressed bax expression and caspase 3 activity, as well as increased bcl-2 expression in H/R-stimulated H9c2 cells. Furthermore, we also found that PMS significantly enhanced the activation of Akt/Nrf2/HO-1 signaling pathway and suppressed the activation of NF-κB signaling pathway in H/R-stimulated H9c2 cells. These results provided substantial evidence that PMS protected against myocardial I/R injury via attenuating oxidative stress, inflammatory response and apoptosis. The protective effects of PMS were attributed to the Akt/Nrf2/HO-1 and NF-κB signaling pathways.

摘要

已发现心肌缺血/再灌注 (I/R) 损伤与氧化应激有关。Plantamajoside (PMS) 是车前草的主要化合物，据报道具有心脏保护和抗氧化作用。目前的研究旨在调查 PMS 对心肌 I/R 损伤的影响。大鼠心肌细胞 H9c2 细胞暴露于缺氧/复氧 (H/R) 以建立体外心肌 I/R 损伤模型。MTT测定证明H/R处理下H9c2细胞活力显着降低，而PMS改善了这种降低。PMS 抑制 H9c2 细胞中 H/R 诱导的 ROS 产生。PMS有效提高了H/R组超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)的活性降低。此外，用 PMS 治疗减弱了 H/R 刺激的 H9c2 细胞中 TNF-α、IL-6 和 IL-1β 的产生。此外，PMS 在 H/R 刺激的 H9c2 细胞中显着抑制 bax 表达和 caspase 3 活性，以及​​增加 bcl-2 表达。此外，我们还发现 PMS 显着增强了 Akt/Nrf2/HO-1 信号通路的激活，并抑制了 H/R 刺激的 H9c2 细胞中 NF-κB 信号通路的激活。通过减轻氧化应激、炎症反应和细胞凋亡。PMS 的保护作用归因于 Akt/Nrf2/HO-1 和 NF-κB 信号通路。