Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, Key laboratory of drug design and optimization, China Pharmaceutical University, No. 24 TongjiaLane, Nanjing, 210009, China.
State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., No. 2 Pujihe East Road, Tianjin, 300410, China.
Sci Rep. 2016 Dec 1;6:37919. doi: 10.1038/srep37919.
The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patterns in plasma and heart tissue. CDDP pretreatment increased energy production, ameliorated biochemical indices, modulated the changes and metabolomic pattern induced by ISO, especially in heart tissue. For the first time, we found that ISO induced myocardial ischemia was accomplished with a reduced fatty acids metabolism and an elevated glycolysis for energy supply upon the ischemic stress; while CDDP pretreatment prevented the tendency induced by ISO and enhanced a metabolic shift towards fatty acids metabolism that conventionally dominates energy supply to cardiac muscle cells. These data suggested that the underlying mechanism of CDDP involved regulating the dominant energy production mode and enhancing a metabolic shift toward fatty acids metabolism in ischemic heart. It was further indicated that CDDP had the potential to prevent myocardial ischemia in clinic.
复方丹参滴丸的持续给药在临床上显示出良好的缓解心肌缺血的疗效。为了探究其潜在的机制，我们使用代谢组学平台评估了在异丙肾上腺素（ISO）诱导的急性心肌缺血大鼠模型中给予 CDDP 后的代谢特征。我们的数据显示，ISO 诱导的动物模型表现出明显的心肌损伤、能量产生减少以及血浆和心脏组织中代谢图谱的明显变化。CDDP 预处理增加了能量产生，改善了生化指标，调节了 ISO 诱导的变化和代谢图谱，尤其是在心脏组织中。我们首次发现，ISO 诱导的心肌缺血是通过减少脂肪酸代谢和增加糖酵解以在缺血应激下提供能量来实现的；而 CDDP 预处理则阻止了 ISO 诱导的这种趋势，并增强了向脂肪酸代谢的代谢转变，而脂肪酸代谢通常是心肌细胞能量供应的主要方式。这些数据表明，CDDP 的作用机制涉及调节主导的能量产生模式，并增强缺血性心脏中的脂肪酸代谢转变。这进一步表明 CDDP 有可能预防临床上的心肌缺血。
