Department of Cardiologya, Traditional Chinese Medicine Hospital of Shaanxi Province, No. 4 Xihuamen Street, Xi'an 710003, China.
Department of Emergency, Xiyuan Hospital, China Academy of Chinese Medical Sciences, No. 1 Xiyuan playground Street, Beijing 100091, China.
Toxicol Appl Pharmacol. 2022 Aug 1;448:116093. doi: 10.1016/j.taap.2022.116093. Epub 2022 May 31.
Ischemic heart disease (IHD) is the primary cause of death worldwide. Salidroside (Sal), the major active compound derived from Rhodiola rosea, is believed to have cardioprotective effects. AMP-activated protein kinase (AMPK), is a pivotal AMP-activated protein kinase in energy metabolism. Whether Sal plays an anti-endoplasmic reticulum stress/mitochondrial fission role through AMPK remains elusive. In this study, we established a myocardial ischemia/reperfusion (I/R) rat model. Rat hearts exposed to Sal with or without compound C were then subjected to I/R. Further, H9c2 cardiomyocytes were subjected to simulated ischemia/reperfusion (SIR) by hypoxia-reoxygenation. The rats and cardiomyocytes were pretreated with Sal, followed by Compound C and AMPK-siRNA to block AMPK activity. We found that Sal significantly ameliorated cardiac function, mitigated infarct size and serum content of lactate dehydrogenase and creatine kinase, improved mitochondrial function, and reduced mitochondrial fission and apoptosis. Furthermore, in cultured H9c2 cardiomyocytes, Sal increased the cell viability and inhibited SIR-induced myocardial apoptosis and mitochondrial fission. Furthermore, the translocation of Drp1 from the cytoplasm to mitochondria induced by salidroside was confirmed both in vivo and in vitro. However, the use of Compound C or AMPK siRNA to block AMPK activity leads to blockade of the protective effects of Sal. In summary, protects against myocardial I/R by activating the AMPK signaling pathway, inhibiting ER stress, and reducing mitochondrial fission and apoptosis.
缺血性心脏病（IHD）是全球主要的死亡原因。红景天苷（Sal）是红景天中主要的活性化合物，被认为具有心脏保护作用。AMP 激活的蛋白激酶（AMPK）是能量代谢中关键的 AMPK。Sal 是否通过 AMPK 发挥抗内质网应激/线粒体分裂作用仍不清楚。在本研究中，我们建立了心肌缺血/再灌注（I/R）大鼠模型。然后，用或不用化合物 C 处理大鼠心脏，使其暴露于 Sal 下，再进行 I/R。此外，通过缺氧复氧使 H9c2 心肌细胞发生模拟缺血/再灌注（SIR）。大鼠和心肌细胞先用 Sal 预处理，然后用 Compound C 和 AMPK-siRNA 阻断 AMPK 活性。我们发现 Sal 显著改善了心脏功能，减轻了梗塞面积和血清乳酸脱氢酶和肌酸激酶含量，改善了线粒体功能，并减少了线粒体分裂和凋亡。此外，在培养的 H9c2 心肌细胞中，Sal 增加了细胞活力，并抑制了 SIR 诱导的心肌细胞凋亡和线粒体分裂。此外，体内和体外均证实 Sal 诱导的 Drp1 从细胞质向线粒体易位。然而，使用 Compound C 或 AMPK siRNA 阻断 AMPK 活性会阻止 Sal 的保护作用。综上所述，Sal 通过激活 AMPK 信号通路、抑制内质网应激以及减少线粒体分裂和凋亡来保护心肌免受 I/R 损伤。
