Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
J Cardiovasc Pharmacol. 2019 Sep;74(3):228-234. doi: 10.1097/FJC.0000000000000710.
Carthamin yellow (CY) is a flavonoid compound isolated from safflower, which is widely used clinically in China. It has various pharmacological effects including promoting blood circulation to remove blood stasis and alleviating pain. Ischemic heart disease is one of the main culprits of illness and death. Here, in this study, ex vivo and in vivo models were used to investigate whether CY reduces ischemia/reperfusion injury. In vitro experiments further verify and explain the potential mechanisms of CY cardioprotective function. Isolated hearts from male rats with or without CY pretreatment before ischemia which underwent 30-minute ischemia followed by 60-minute reperfusion showed that CY pretreatment significantly reduced the infarct size and lactate dehydrogenase release. The in vivo experiments also indicated CY preadministration (i.v.) reduced infarct size and improved the heart function, which was impaired by myocardial ischemia/reperfusion injury. The in vitro model on myocardial cell also showed that CY reduced ischemia/reperfusion injury by reducing the lactate dehydrogenase and reactive oxygen species (ROS) releasing. Eliminating ROS with N-acetylcysteine or preinject CY into rat jugular vein reduces the expression of IL-6, TNF-a, and, especially, IL-1b in an in vivo I/R model. Also, CY pretreatment strongly reduces ischemia/reperfusion-induced NLRP3 up-expression and caspase-1 activation. Our results indicated CY reduced ischemia-reperfusion injury when administered before reperfusion. The reduction in injury is accompanied by a reduced ROS release and decreased inflammatory response.
红花黄色素(CY)是从红花中分离得到的一种黄酮类化合物,在中国临床应用广泛。它具有多种药理作用,包括促进血液循环、祛瘀止痛。缺血性心脏病是疾病和死亡的主要罪魁祸首之一。在这项研究中,使用了离体和在体模型来研究 CY 是否减轻缺血/再灌注损伤。体外实验进一步验证和解释了 CY 心脏保护功能的潜在机制。在有或没有 CY 预处理的雄性大鼠离体心脏中,进行 30 分钟缺血,然后进行 60 分钟再灌注,结果显示 CY 预处理显著减少了梗死面积和乳酸脱氢酶的释放。体内实验也表明,CY 预处理(静脉注射)减少了梗死面积并改善了因心肌缺血/再灌注损伤而受损的心脏功能。心肌细胞的体外模型也表明,CY 通过减少乳酸脱氢酶和活性氧(ROS)的释放来减轻缺血/再灌注损伤。用 N-乙酰半胱氨酸消除 ROS 或预先将 CY 注入大鼠颈静脉,可降低体内 I/R 模型中 IL-6、TNF-a,特别是 IL-1b 的表达。此外,CY 预处理可强烈降低缺血/再灌注诱导的 NLRP3 表达上调和半胱天冬酶-1 激活。我们的结果表明,CY 在再灌注前给药可减轻缺血/再灌注损伤。损伤的减少伴随着 ROS 释放减少和炎症反应降低。