Supplementary Material for: Panax Quinquefolium Saponins Attenuate Myocardial Dysfunction Induced by Chronic Ischemia

<b><i>Background/Aims:</i></b> Previous studies in rat models of myocardial ischemia showed that Panax quinquefolium saponins (PQS) could attenuate ischemic/reperfusion injury, increase vessel density and improve cardiac function. In the current study, we examined whether PQS could attenuate myocardial dysfunction in a swine model of chronic myocardial ischemia (CMI). <b><i>Methods:</i></b> CMI was established in Bama mini-pigs by placing amroid constrictor on the left anterior descending artery (LAD). Starting from 2 months after the surgery, pigs randomly received PQS (30 mg/kg/day), atorvastatin (1.5 mg/kg/day), or no drug for one month (n=6). A group of pigs receiving sham surgery was included as an additional control. Glucose utilization was assessed with positron emission tomography-computer tomography (PET-CT). Cardiac function was assessed with echocardiography. Myocyte size, nuclear density, and arteriolar density were examined in tissue section obtained from the ischemia area. Potential molecular targets of PQS were identified using proteomic analysis with isobaric tags for relative and absolute quantitation (iTARQ) and network pharmacology. <b><i>Results:</i></b> In comparison to the sham controls, pigs implanted with ameroid constrictor had decreased ventricular wall motion, left ventricular ejection fraction (LVEF), and glucose utilization. PQS significantly increased cardiac function and glucose utilization. Arteriole density and myocyte nuclear density were increased. Myocyte diameter was decreased. PQS also attenuated the CMI-induced change of protein expression profile. The effects of atorvastatin were generally similar to that of PQS. However, PQS attenuated the reduction of left ventricular systolic WT induced by CMI more robustly than atorvastatin. <b><i>Conclusion:</i></b> The results from the current study supports the use of PQS in patients with coronary artery disease.

<b><i>背景与目的：</i></b> 既往针对大鼠心肌缺血模型的研究显示，西洋参皂苷（Panax quinquefolium saponins, PQS）可减轻缺血/再灌注损伤、提升血管密度并改善心功能。本研究旨在探究西洋参皂苷是否可改善慢性心肌缺血（chronic myocardial ischemia, CMI）巴马小型猪模型的心肌功能障碍。<br><br><b><i>方法：</i></b> 本研究通过在巴马小型猪的左前降支动脉（left anterior descending artery, LAD）放置Ameroid缩窄环（amroid constrictor）构建慢性心肌缺血模型。术后2个月起，将猪只随机分为三组，分别予以西洋参皂苷（30 mg/kg/天）、阿托伐他汀（1.5 mg/kg/天）或不予药物干预，干预周期为1个月，每组6只动物。另设假手术组作为额外对照。采用正电子发射断层显像-计算机断层扫描（positron emission tomography-computer tomography, PET-CT）评估葡萄糖代谢水平，通过超声心动图检测心功能。对缺血区域获取的组织切片开展心肌细胞大小、细胞核密度及小动脉密度的检测。采用同量异位素相对与绝对定量（isobaric tags for relative and absolute quantitation, iTRAQ，原文笔误为iTARQ）蛋白质组学分析与网络药理学，鉴定西洋参皂苷的潜在分子靶点。<br><br><b><i>结果：</i></b> 与假手术组相比，植入Ameroid缩窄环的猪只出现心室壁运动减弱、左心室射血分数（left ventricular ejection fraction, LVEF）降低及葡萄糖代谢水平下降。西洋参皂苷可显著提升心功能与葡萄糖代谢水平，升高小动脉密度与心肌细胞核密度，同时缩小心肌细胞直径。此外，西洋参皂苷可改善慢性心肌缺血诱导的蛋白质表达谱异常改变。阿托伐他汀的作用与西洋参皂苷整体相似，但西洋参皂苷较阿托伐他汀更显著地改善了慢性心肌缺血诱导的左心室收缩期室壁厚度降低。<br><br><b><i>结论：</i></b> 本研究结果支持将西洋参皂苷应用于冠状动脉粥样硬化性心脏病患者的临床治疗。