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Astragaloside IV attenuates chronic intermittent hypoxia-induced myocardial injury by modulating Ca2+ homeostasis.
Cell Biochemistry and Function ( IF 2.8 ) Pub Date : 2020-04-19 , DOI: 10.1002/cbf.3538
Shan Jiang 1 , Guangyu Jiao 1 , Yunqiu Chen 1 , Mingxin Han 1 , Xinzhuo Wang 1 , Wenjuan Liu 1
Affiliation  

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 Ca2+ 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 Ca2+ and altered expressions of Ca2+ 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 Ca2+ homeostasis to inhibit apoptosis, protecting against CIH‐induced myocardial injury eventually, suggesting it may be a potential agent for cardiac damage of OSAS patients.

中文翻译:

黄芪甲苷IV通过调节Ca2 +稳态来减轻慢性间歇性缺氧引起的心肌损伤。

阻塞性睡眠呼吸暂停综合症(OSAS)是慢性间歇性缺氧(CIH)的重要结果。黄芪甲苷IV(AS-IV)在多种疾病中具有多种保护作用。但是,尚不清楚AS-IV是否能减轻CIH诱发的心肌损伤。在这项研究中,建立了暴露于CIH的大鼠,并用AS-IV治疗4周。在体外,将经过CIH暴露的H9C2心肌细胞用AS-IV处理48小时。然后是心脏功能,形态,纤维化,凋亡和Ca 2+确定稳态以评估心脏损害。结果表明,AS-IV可减轻CIH大鼠的心脏功能障碍和组织学损害。AS-IV可减少CIH大鼠的TUNEL阳性细胞和活化的凋亡蛋白。我们还注意到,在CIH暴露下,AS-IV逆转了Ca 2+的积累并改变了Ca 2+处理蛋白的表达(SERCA2a和RYR2的减少,以及p-CaMKII和NCX1的增加)。此外,AS-IV可增加CIH诱导的SERCA2a活性降低。在H9C2细胞中也观察到了相似的结果。总而言之,这些发现表明AS-IV调节Ca 2+ 稳态可抑制细胞凋亡,最终防止CIH引起的心肌损伤,表明它可能是OSAS患者心脏损害的潜在药物。
更新日期:2020-04-19
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