Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Cell Biochem Funct. 2020 Aug;38(6):710-720. doi: 10.1002/cbf.3538. Epub 2020 Apr 19.
Obstructive sleep apnea syndrome (OSAS) is an important consequence of chronic intermittent hypoxia (CIH). Astragaloside IV (AS-IV) exerts multiple protective effects in diverse diseases. However, whether AS-IV can attenuate CIH-induced myocardial injury is unclear. In this study, rats exposed to CIH were established and treated with AS-IV for 4 weeks. In vitro, H9C2 cardiomyocytes subjected to CIH exposure were treated with AS-IV for 48 hours. Then the cardiac function, morphology, fibrosis, apoptosis and Ca homeostasis were determined to assess cardiac damage. Results showed that AS-IV attenuated cardiac dysfunction and histological lesions in CIH rats. The increased TUNEL-positive cells and activated apoptotic proteins in CIH rats were reduced by AS-IV. We also noticed that AS-IV reversed the accumulation of Ca and altered expressions of Ca handling proteins (decreases of SERCA2a and RYR2, and increases of p-CaMKII and NCX1) under CIH exposure. Furthermore, CIH-induced reduction of SERCA2a activity was increased by AS-IV in rats. Similar results were also observed in H9C2 cells. Altogether, these findings indicate that AS-IV modulates Ca homeostasis to inhibit apoptosis, protecting against CIH-induced myocardial injury eventually, suggesting it may be a potential agent for cardiac damage of OSAS patients. SIGNIFICANCE OF THE STUDY: Chronic intermittent hypoxia (CIH) is a great contributor of OSAS, which is closely associated with cardiovascular diseases. It is necessary for developing a promising drug to attenuate CIH-induced myocardial injury. This work suggests that AS-IV can attenuate myocardial apoptosis and calcium disruption, thus protecting against CIH-induced myocardial injury. It may represent a novel therapeutic for cardiac damage of OSAS.
阻塞性睡眠呼吸暂停综合征（OSAS）是慢性间歇性低氧（CIH）的重要后果。黄芪甲苷 IV（AS-IV）在多种疾病中发挥多种保护作用。然而，AS-IV 是否能减轻 CIH 引起的心肌损伤尚不清楚。在这项研究中，建立了慢性间歇性低氧（CIH）暴露的大鼠模型，并给予 AS-IV 治疗 4 周。在体外，将 H9C2 心肌细胞暴露于 CIH 下，并用 AS-IV 处理 48 小时。然后测定心脏功能、形态、纤维化、凋亡和钙稳态，以评估心脏损伤。结果表明，AS-IV 减轻了 CIH 大鼠的心脏功能障碍和组织学损伤。AS-IV 减少了 CIH 大鼠中 TUNEL 阳性细胞和激活的凋亡蛋白。我们还注意到，AS-IV 逆转了 CIH 暴露下钙的积累和钙处理蛋白的表达改变（SERCA2a 和 RYR2 减少，p-CaMKII 和 NCX1 增加）。此外，AS-IV 增加了 CIH 大鼠中 SERCA2a 活性的降低。在 H9C2 细胞中也观察到了类似的结果。总之，这些发现表明 AS-IV 调节钙稳态以抑制细胞凋亡，最终防止 CIH 引起的心肌损伤，表明它可能是 OSAS 患者心脏损伤的潜在药物。
慢性间歇性低氧（CIH）是 OSAS 的主要原因，与心血管疾病密切相关。开发一种有前途的药物来减轻 CIH 引起的心肌损伤是必要的。这项工作表明，AS-IV 可以减轻心肌细胞凋亡和钙紊乱，从而防止 CIH 引起的心肌损伤。它可能代表了 OSAS 心脏损伤的一种新的治疗方法。
