Guo Ming, Liu Jiangang, Guo Feifei, Shi Junhe, Wang Chenglong, Bible Paul W, Yang Minfu, Tian Yi, Wei Lai, Wang Peili, Shi Dazhuo
Cardiovascular Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Cell Physiol Biochem. 2018;49(4):1277-1288. doi: 10.1159/000493407. Epub 2018 Sep 11.
BACKGROUND/AIMS: 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).
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.
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.
The results from the current study supports the use of PQS in patients with coronary artery disease.
背景/目的：先前在大鼠心肌缺血模型中的研究表明，西洋参皂苷（PQS）可减轻缺血/再灌注损伤，增加血管密度并改善心脏功能。在本研究中，我们检测了PQS是否能减轻慢性心肌缺血（CMI）猪模型中的心肌功能障碍。
通过在巴马小型猪的左前降支动脉（LAD）放置阿霉素环来建立CMI模型。从手术后2个月开始，猪随机接受PQS（30mg/kg/天）、阿托伐他汀（1.5mg/kg/天）或不接受药物治疗1个月（n = 6）。另一组接受假手术的猪作为额外对照。用正电子发射断层扫描-计算机断层扫描（PET-CT）评估葡萄糖利用情况。用超声心动图评估心脏功能。在从缺血区域获取的组织切片中检查心肌细胞大小、核密度和小动脉密度。使用相对和绝对定量等压标签（iTARQ）蛋白质组学分析和网络药理学确定PQS的潜在分子靶点。
与假手术对照组相比，植入阿霉素环的猪心室壁运动、左心室射血分数（LVEF）和葡萄糖利用均降低。PQS显著改善心脏功能和葡萄糖利用。小动脉密度和心肌细胞核密度增加。心肌细胞直径减小。PQS还减弱了CMI诱导的蛋白质表达谱变化。阿托伐他汀的作用通常与PQS相似。然而，PQS比阿托伐他汀更有力地减轻了CMI诱导的左心室收缩期WT的降低。
本研究结果支持PQS用于冠心病患者。
