Panax Quinquefolium Saponins Attenuate Myocardial Dysfunction Induced by Chronic Ischemia
Panax Quinquefolium Saponins Attenuate Myocardial Dysfunction Induced by Chronic Ischemia
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西洋参皂苷减轻慢性缺血引起的心肌功能障碍
DOI：
10.1159/000493407
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Shi, Dazhuo
中科院分区：
文献类型：
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作者：
Guo, Ming;Liu, Jiangang;Shi, Dazhuo
背景/目的：之前对大鼠心肌缺血模型的研究表明，西洋参皂苷（PQS）可以减轻缺血/再灌注损伤，增加血管密度，改善心功能。在当前的研究中，我们检查了 PQS 是否可以减轻慢性心肌缺血 (CMI) 猪模型中的心肌功能障碍。方法：通过在巴马小型猪左前降支（LAD）上放置阿莫罗缩窄器来建立CMI。从术后2个月开始，猪随机接受PQS（30 mg/kg/天）、阿托伐他汀（1.5 mg/kg/天）或1个月不用药（n=6）。一组接受假手术的猪被纳入作为额外的对照。通过正电子发射断层扫描-计算机断层扫描（PET-CT）评估葡萄糖利用率。通过超声心动图评估心脏功能。在从缺血区域获得的组织切片中检查肌细胞大小、核密度和动脉密度。使用用于相对和绝对定量 (iTARQ) 的同量异序标签的蛋白质组学分析和网络药理学来鉴定 PQS 的潜在分子靶点。结果：与假手术对照组相比，植入 ameroid 缩窄器的猪心室壁运动、左心室射血分数 (LVEF) 和葡萄糖利用率降低。 PQS 显着提高了心脏功能和葡萄糖利用率。小动脉密度和肌细胞核密度增加。肌细胞直径减小。 PQS 还减弱了 CMI 诱导的蛋白质表达谱变化。阿托伐他汀的作用总体上与 PQS 相似。然而，PQS 比阿托伐他汀更能减弱 CMI 引起的左心室收缩期 WT 的降低。结论：当前研究的结果支持 PQS 在冠状动脉疾病患者中的应用。
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). Methods: 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. Results: 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. Conclusion: The results from the current study supports the use of PQS in patients with coronary artery disease.