Laboratory of Chinese Drug Pharmacology, College of Medical Sciences, China Three Gorges University, Yichang, PR China.
J Ethnopharmacol. 2012 Mar 6;140(1):73-82. doi: 10.1016/j.jep.2011.12.024. Epub 2011 Dec 31.
To study the cardioprotective effects of saponins from Panax japonicus (SPJ) on acute myocardial ischemia injury rats induced by ligating of the left anterior descending branch (LAD), on the basis of this investigation, the possible mechanism of SPJ was elucidated.
SPJ was identified by high performance liquid chromatography-evaporative light scattering detection. Male Sprague-Dawley rats (200-220g) were randomly divided into four groups: sham-operated, LAD, LAD+l-SPJ (SPJ, 50mg/kg/day, orally) and LAD+h-SPJ (SPJ, 100mg/kg/day, orally). Before operation, the foregoing groups were pretreated with homologous drug once a day for 7 days, respectively. After twelve hours in LAD, the cardioprotective effects of SPJ were evaluated by infarct size, biochemical values, hemodynamic, and histopathological observations and the antioxidative and antiapoptotic relative gene expressions.
SPJ significantly improved heart function and decreased infarct size; remarkably decreased levels of serum lactate dehydrogenase, creatine kinase, xanthine oxide and malondialdehyde content, increased contents of serum total antioxidant capacity, superoxide dismutase (SOD), glutathione peroxidase, catalase; quantitative real-time PCR results showed that SPJ might markedly reverse the down-regulated mRNA expressions of the SOD1, SOD2 and SOD3, ameliorate the increased Bax and caspase-3 mRNA expressions and decreased Bcl-2 mRNA expression and ratios of Bcl-2 to Bax. Histopathological observations provided supportive evidence for biochemical analyses, and with the dose of SPJ increasing, the aforesaid improvement became more and more strong.
The studies demonstrated that in ischemic myocardium, oxidative stress caused the overgeneration and accumulation of reactive oxygen species (ROS), which was central of cardiac ischemic injury. SPJ exerted beneficially cardioprotective effects on myocardial ischemia injury rats, mainly scavenging oxidative stress-triggered overgeneration and accumulation of ROS, alleviating myocardial ischemia injury and cardiac cell death.
基于此研究，探讨西洋参总皂苷（SPJ）对结扎左前降支（LAD）所致急性心肌缺血损伤大鼠的心脏保护作用，并阐明其可能的作用机制。
采用高效液相色谱-蒸发光散射检测法鉴定 SPJ。雄性 Sprague-Dawley 大鼠（200-220g）随机分为 4 组：假手术组、LAD 组、LAD+低剂量 SPJ（SPJ，50mg/kg/天，灌胃）组和 LAD+高剂量 SPJ（SPJ，100mg/kg/天，灌胃）组。术前，上述各组分别每日给予同源药物预处理 1 次，共 7 天。结扎 LAD 12 小时后，通过梗死面积、生化值、血流动力学和组织病理学观察以及抗氧化和抗凋亡相关基因表达，评价 SPJ 的心脏保护作用。
SPJ 显著改善心功能，减少梗死面积；显著降低血清乳酸脱氢酶、肌酸激酶、黄嘌呤氧化酶和丙二醛含量，增加血清总抗氧化能力、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶、过氧化氢酶含量；实时定量 PCR 结果显示，SPJ 可能显著逆转 SOD1、SOD2 和 SOD3 的下调 mRNA 表达，改善 Bax 和 caspase-3 mRNA 表达的增加以及 Bcl-2 mRNA 表达和 Bcl-2/Bax 比值的降低。组织病理学观察为生化分析提供了支持性证据，并且随着 SPJ 剂量的增加，上述改善作用变得越来越强。
研究表明，在缺血性心肌中，氧化应激导致活性氧（ROS）的过度产生和积累，这是心脏缺血损伤的核心。SPJ 对心肌缺血损伤大鼠发挥有益的心脏保护作用，主要通过清除氧化应激触发的 ROS 过度产生和积累，减轻心肌缺血损伤和心肌细胞死亡。
