人参不定根乙醇提取物保护异丙肾上腺素诱导的心肌缺血作用研究

Study on the positive effects of the ethanol extract of ginseng adventitious roots on the isoproterenol-induced myocardial ischemia

中文关键词:  人参不定根  心肌缺血  人参皂苷  氧化应激  半胱天冬酶-1

英文关键词:Ginseng adventitious root  myocardial ischemia  ginsenoside  oxidative stress  caspase-1

中文摘要:

      目的 研究人参不定根(ginseng adventitious roots, GAR)提取物对异丙肾上腺素(isoproterenol, ISO)诱导的小鼠心肌缺血损伤的保护作用。方法 50只C57BL/6小鼠随机分为5组(n=10), 包括对照组、ISO组、低剂量GAR+ISO组, 高剂量GAR+ISO组、高剂量GAR组, 连续灌胃28 d, 在第27、28 d皮下注射ISO建立小鼠心肌缺血模型(对照组与高剂量GAR组注射同剂量生理盐水)。检测小鼠体重、心重、心重体重比和心电图变化, 苏木精—伊红染色法染色检测心脏组织病理学改变, 试剂盒检测心肌损伤相关酶及抗氧化相关酶活性, 蛋白质印迹法检测炎症相关蛋白半胱天冬酶-1 (caspase-1)及白介素-1β (interleukin-1, IL-1β)表达变化。结果 GAR预保护显著降低ISO导致的ST段升高和心重体重比增加, 降低血清中心肌损伤相关酶乳酸脱氢酶、肌酸激酶同工酶、谷丙转氨酶和心肌肌钙蛋白T水平, 明显提高心肌组织抗氧化相关酶超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶活性。组织病理学分析也显示GAR能够减轻心肌损伤, 通过蛋白质印记分析发现GAR明显减少炎症通路caspase-1、IL-1β蛋白表达。通过相同实验检测高剂量GAR组对正常机体组织病理及各类生化指标无任何明显损伤作用。结论 GAR对ISO导致的心脏损伤具有明显的保护作用, 其机制可能是增强内源性抗氧化能力及减少炎症蛋白表达。

英文摘要:

      Objective To investigate the protective effects of ginseng adventitious roots (GAR) on isoproterenol (ISO)-induced myocardial ischemia injury to mice. Methods Fifty C57BL/6 mice were randomly divided into 5 groups (n=10), including control group, ISO group, low dose GAR+ISO group, high dose GAR+ISO group and high dose GAR group, with continuous gavage for 28 days; the mouse myocardial ischemia model was established by subcutaneous injection of ISO on the 27th and 28th day (the control group and high dose GAR group were injected with the same dose of normal saline). Then, the changes of body weight, heart weight, heart weight to weight ratio and electrocardiogram changes were detected. The histopathological changes of the heart were detected by hematoxylin-eosin staining. The activities of myocardial damage-related enzymes and antioxidant enzymes were detected by the kit. Western blot was also used to detect the changes of inflammatory proteins caspase-1 and interleukin-1β (IL-1β). Results The pretreatment with high dose GAR+ISO group significantly reduced ISO-induced ST-segment elevation and increased heart weight to weight ratio, decreased the levels of lactate dehydrogenase, creatine kinase, alanine aminotransferase, and cardiac troponin T in serum, and obviously enhanced the activities of superoxide dismutase, glutathione peroxidase, and catalase in heart tissue. Histopathological analysis also showed that GAR could alleviate myocardial injury induced by ISO, and western blot analysis showed that GAR could significantly reduce inflammatory pathway-related proteins including caspase-1, cleaved-caspase-1, and IL-1β. The same experiment was conducted to detect that the high dose GAR group had no obvious damage to histopathology and biochemical indexes of normal body. Conclusion Therefore, taken together, GAR has a significant protective effect on ISO-induced cardiac injury, possibly through enhancing endogenous oxidation resistance and reducing inflammatory protein expression.