High glucose (HG)‐induced cardiomyocytes (CMs) injury is a leading cause of diabetic cardiomyopathy with little treatment options. Irisin, a new myokine, which is cleaved from its precursor fibronectin type III domain‐containing protein 5 (FNDC5), has aroused great attention as an essential cardioprotective factor and glucose metabolism regulator but little was known on diabetic cardiomyopathy yet. Here, we aim to clarify the role of irisin in the HG‐induced CMs injury. Neonatal Sprague–Dawley rat CMs were cultured in a normal or HG medium for 12, 24, and 48 hr, respectively before exposing to irisin. The apoptosis level was determined by terminal‐deoxynucleotidyl transferase‐mediated‐dUTP nick end‐labeling assay. Cell viability was measured with the conventional methyl thiazolyl tetrazolium assay. Moreover, reactive oxygen species production was evaluated by dihydroethidium staining. Inflammatory factors, namely tumor necrosis factor‐α, interleukin‐6, interleukin‐1β were determined by enzyme‐linked immunosorbent assay kits. Furthermore, protein and messenger RNA (mRNA) expressions were measured by western blot and quantitative real‐time polymerase chain reaction, respectively. HG increases the apoptosis of CMs and activated the inflammatory responses and oxidative stress in CMs. Meanwhile, the mRNA and protein expressions of FNDC5 are decreased after HG exposure. Nevertheless, the increased apoptosis is alleviated by irisin treatment. Notably, irisin suppresses the inflammatory responses and oxidative stress in injured CMs. Mechanically, after the administration of Compound C, AMP‐activated protein kinase (AMPK) inhibitor, these cardioprotective effects resulting from irisin are reversed. Irisin plays a significant role in antiapoptosis, anti‐inflammation, antioxidative stress in HG‐induced CMs via AMPK/mammalian target of the rapamycin signaling pathway.

中文翻译：

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Irisin通过AMPK / mTOR信号通路改善了高糖诱导的心肌细胞损伤。

高糖（HG）诱导的心肌细胞（CMs）损伤是糖尿病性心肌病的主要原因，几乎没有治疗选择。Irisin是一种新的肌动蛋白，它从其前体纤连蛋白III型结构域蛋白5（FNDC5）裂解而来，作为一种重要的心脏保护因子和葡萄糖代谢调节剂引起了广泛关注，但对糖尿病性心肌病知之甚少。在这里，我们旨在阐明虹膜素在HG诱导的CMs损伤中的作用。暴露于虹膜素之前，分别在普通或HG培养基中培养新生Sprague–Dawley大鼠CM 12、24和48小时。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法测定细胞凋亡水平。用常规的甲基噻唑基四唑鎓测定法测量细胞活力。此外，通过二氢乙锭染色评估活性氧的产生。用酶联免疫吸附试剂盒测定炎症因子，即肿瘤坏死因子-α，白介素-6，白介素-1β。此外，分别通过蛋白质印迹和定量实时聚合酶链反应测量蛋白质和信使RNA（mRNA）的表达。HG增加了CM的凋亡并激活了CM的炎症反应和氧化应激。同时，暴露于HG后，FNDC5的mRNA和蛋白表达降低。然而，通过虹膜素治疗减轻了增加的细胞凋亡。值得注意的是，虹膜素抑制受伤的CM中的炎症反应和氧化应激。机械上，在给予化合物C，AMP激活的蛋白激酶（AMPK）抑制剂后，这些由虹膜素产生的心脏保护作用被逆转。虹膜素通过AMPK /雷帕霉素信号传导途径的哺乳动物靶点在HG诱导的CMs的抗凋亡，抗炎，抗氧化应激中起重要作用。