Department of Pharmacy, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
School of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China.
Int J Mol Med. 2018 Nov;42(5):2628-2640. doi: 10.3892/ijmm.2018.3844. Epub 2018 Aug 27.
Traditional Chinese medicines, including Radix Salvia miltiorrhiza (SM) and Lignum Dalbergia odorifera (DO) extracts, have historically been used to treat myocardial ischemia and other cardiovascular diseases. The volatile oil of DO (DOO) is one of the main components of DO. The aim of the present study was to assess the cardioprotective effects and possible underlying mechanisms of SM‑DOO in pigs with ameroid constriction‑induced chronic myocardial ischemia. An ameroid constrictor was placed around the left anterior descending coronary artery of pigs to induce chronic myocardial ischemia. At weeks 2, 6 and 8, myocardial injury markers and blood gas levels were detected. At week 8, coronary angiography, echocardiography and hemodynamics analysis were performed to evaluate myocardial function. Following sacrifice, myocardial tissue was collected and subjected to morphological, histopathological and apoptosis assays. Western blotting was used to detect the protein expression of Bcl‑2 associated X (Bax), Bcl‑2, Akt, phosphorylated (p)‑Akt, glycogen synthase kinase (GSK)‑3β and p‑GSK‑3β. It was revealed that SM‑DOO treatment following chronic myocardial ischemia significantly downregulated the expression of myocardial injury markers, ameliorated myocardial oxygen consumption, increased collateralization, reduced regional cardiac dysfunction and limited the extent of myocardial damage. Furthermore, the results of an apoptosis assay revealed that the apoptosis rate was decreased, the expression of Bax decreased and Bcl‑2 increased, and the ratio of Bcl‑2/Bax was increased. Further experiments indicated that treatment with SM‑DOO increased the phosphorylation of Akt and GSK‑3β. These findings suggest that SM‑DOO treatment ameliorates myocardial injury in a chronic myocardial ischemia model, and that the underlying mechanisms responsible may be associated with the activation of the Akt/GSK‑3β signal pathway. Thus, experimental evidence that SM‑DOO may be an effective drug for the prevention and treatment of chronic myocardial ischemia in clinical applications has been provided.
传统中药，包括丹参和降香提取物，历来被用于治疗心肌缺血和其他心血管疾病。降香的挥发油（DOO）是降香的主要成分之一。本研究旨在评估丹参-降香挥发油（SM-DOO）在猪肥厚型心肌病模型中的心脏保护作用及其可能的机制。在猪的左前降支冠状动脉周围放置一种缩窄环，以诱导慢性心肌缺血。在第 2、6 和 8 周时，检测心肌损伤标志物和血气水平。在第 8 周时，进行冠状动脉造影、超声心动图和血流动力学分析，以评估心肌功能。处死动物后，采集心肌组织进行形态学、组织病理学和凋亡检测。Western blot 检测 Bcl-2 相关 X（Bax）、Bcl-2、Akt、磷酸化（p）-Akt、糖原合成酶激酶（GSK）-3β和 p-GSK-3β的蛋白表达。结果表明，慢性心肌缺血后给予 SM-DOO 治疗可显著下调心肌损伤标志物的表达，改善心肌耗氧量，增加侧支循环，减轻区域性心功能障碍，限制心肌损伤程度。此外，凋亡检测结果显示，细胞凋亡率降低，Bax 表达降低，Bcl-2 表达增加，Bcl-2/Bax 比值增加。进一步的实验表明，SM-DOO 治疗可增加 Akt 和 GSK-3β的磷酸化。这些发现表明，SM-DOO 治疗可改善慢性心肌缺血模型中的心肌损伤，其作用机制可能与激活 Akt/GSK-3β信号通路有关。因此，为 SM-DOO 可能成为临床应用中预防和治疗慢性心肌缺血的有效药物提供了实验依据。
