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Danshen‐Enhanced Cardioprotective Effect of Cardioplegia on Ischemia Reperfusion Injury in a Human‐Induced Pluripotent Stem Cell‐Derived Cardiomyocytes Model

诱导多能干细胞 再灌注损伤 缺血 缺氧(环境) 生物学中的钙 细胞凋亡 活性氧 心肌保护 医学 抗氧化剂 心脏病学 药理学 化学 内科学 氧气 胚胎干细胞 生物化学 有机化学 基因
作者
Wei Wei,Yiwei Liu,Qiang Zhang,Yangming Wang,Xiaoling Zhang,Hao Zhang
出处
期刊:Artificial Organs [Wiley]
卷期号:41 (5): 452-460 被引量:25
标识
DOI:10.1111/aor.12801
摘要

Myocardial ischemia-reperfusion (I/R) injury is unavoidable during cardioplegic arrest and open-heart surgery. Danshen is one of the most popular traditional herbal medicines in China, which has entered the Food and Drug Administration-approved phase III clinical trial. This study was aimed to develop a human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) model to mimic I/R injury and evaluate the cardioprotective effect of regular cardioplegic solution with Danshen. hiPSC-CMs were cultured with the crystalloid cardioplegic solution (Thomas group) and Thomas solution with 2 or 10 µg/mL Danshen (Thomas plus Danshen groups). The cells under normoxic culture condition served as baseline group. Then, the cells were placed in a modular incubator chamber. After 45 min hypoxia and 3 h reoxygenation, hiPSC-CMs subjected to hypoxia/reoxygenation resulted in a sharp increase of reactive oxygen species (ROS) content in Thomas group versus baseline group. Compared with the Thomas group, ROS accumulation was significant suppressed in Thomas plus Danshen groups, which might result from elevating the content of glutathione and enhanced activities of superoxide dismutase and glutathione peroxidase. The enhanced L-type Ca2+ current in hiPSC-CMs after I/R injury was also significantly decreased by Danshen, and meanwhile intracellular Ca2+ level was reduced and calcium overload was suppressed. Thomas plus Danshen groups also presented less irregular transients and lower apoptosis rates. As a result, Danshen could improve antioxidant and calcium handling in cardiomyocytes during I/R and lead to reduced arrhythmia events and apoptosis rates. hiPSC-CMs model offered a platform for the future translational study of the cardioplegia.
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