Emergency Department, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
Cell Transplant. 2020 Jan-Dec;29:963689720967672. doi: 10.1177/0963689720967672.
Myocardial infarction (MI) is one of the most serious cardiovascular diseases associated with myocardial ischemia/reperfusion (I/R) injury. Glaucocalyxin A (GLA) is a biologically active ent-kauranoid diterpenoid that has been found to ameliorate myocardial I/R injury in mice. However, the mechanism has not been fully investigated. In the present study, we aimed to investigate the effect of GLA on rat cardiomyocytes H9c2 cells exposed to hypoxia/reoxygenation (H/R). The results showed that GLA treatment improved cell viability of H/R-stimulated H9c2 cells. Administration with GLA suppressed the H/R-stimulated reactive oxygen species (ROS) production in H9c2 cells. GLA also elevated the activities of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase in H/R-stimulated H9c2 cells. Moreover, GLA prevented H/R-stimulated cell apoptosis in H9c2 cells, as evidenced by increased bcl-2 expression, decreased bax expression, as well as reduced caspase-3 activity. Furthermore, GLA enhanced the activation of protein kinase B (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in H9c2 cells exposed to H/R. Additionally, treatment with LY294002 reserved the protective effects of GLA on H/R-stimulated oxidative injury in H9c2 cells. In conclusion, these findings suggested that GLA protected H9c2 cells from H/R-stimulated oxidative damage, which was mediated by the Akt/Nrf2/HO-1 signaling pathway. Thus, GLA might be a promising therapeutic agent for the prevention and treatment of myocardial I/R.
心肌梗死（MI）是与心肌缺血/再灌注（I/R）损伤相关的最严重的心血管疾病之一。蓝萼甲素（GLA）是一种具有生物活性的-ent-贝壳杉烷二萜，已被发现可改善小鼠心肌 I/R 损伤。然而，其机制尚未完全研究清楚。在本研究中，我们旨在研究 GLA 对缺氧/复氧（H/R）刺激的大鼠心肌 H9c2 细胞的影响。结果表明，GLA 处理可提高 H/R 刺激的 H9c2 细胞的细胞活力。给予 GLA 可抑制 H/R 刺激的 H9c2 细胞中活性氧（ROS）的产生。GLA 还可提高 H/R 刺激的 H9c2 细胞中抗氧化酶的活性，包括超氧化物歧化酶和谷胱甘肽过氧化物酶。此外，GLA 可防止 H/R 刺激的 H9c2 细胞凋亡，表现为 bcl-2 表达增加、bax 表达减少以及 caspase-3 活性降低。此外，GLA 可增强 H/R 刺激的 H9c2 细胞中蛋白激酶 B（Akt）/核因子红细胞 2 相关因子 2（Nrf2）/血红素加氧酶-1（HO-1）信号通路的激活。此外，用 LY294002 处理可保留 GLA 对 H/R 刺激的 H9c2 细胞氧化损伤的保护作用。总之，这些发现表明，GLA 通过 Akt/Nrf2/HO-1 信号通路保护 H9c2 细胞免受 H/R 刺激的氧化损伤。因此，GLA 可能是预防和治疗心肌 I/R 的有前途的治疗剂。
