珠子参总皂苷对大鼠心肌缺血/再灌注损伤的保护作用及机制研究

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (11): 1224-1232.

珠子参总皂苷对大鼠心肌缺血/再灌注损伤的保护作用及机制研究

刘爱华¹, 石孟琼¹, 杨文雁¹, 颜为红¹, 龚学谦¹, 熊焱强¹, 周继刚², 罗涛², 张继红²

¹三峡大学医学院,宜昌 443002,湖北;
²三峡大学中医临床医学院内科住院部,宜昌 443002,湖北

收稿日期:2012-10-16 修回日期:2013-04-12 出版日期:2013-11-26 发布日期:2013-11-22
通讯作者: 石孟琼,女,本科,实验师,研究方向:心脑血管药理。Tel: 0717-6396818 E-mail: shmq0212@126.com
作者简介:刘爱华,女,本科,实验师,研究方向:组织形态学。Tel: 0717-6396818 E-mail: 455213374@qq.com

Cardioprotective effect and its mechanism of total saponin from Panacis majoris rhizoma on myocardium ischemia/reperfusion injury in rats

LIU Ai-hua¹, SHI Meng-qiong¹, YAN Wen-yan¹, YANG Wei-hong¹, GONG Xue-qian¹, XIONG Yan-qiang¹, ZHOU Ji-gang², LUO Tao², ZHANG Ji-hong²

¹Medical Science College, China Three Gorges University, Yichang 443002, Hubei, China;
²Medical Inpatient Department, Traditional Chinese Medicine Clinical Hospital, China Three Gorges University, Yichang 443002, Hubei, China

Received:2012-10-16 Revised:2013-04-12 Online:2013-11-26 Published:2013-11-22

摘要/Abstract

摘要： 目的: 研究珠子参总皂苷预处理对大鼠心肌缺血再灌注损伤(Myocardium ischemia/Reperfusion injury, MI/RI)的保护作用及可能的作用机制。方法: 实验大鼠随机分为假手术组、缺血/再灌注模型组、珠子参总皂苷100 和 200 mg/kg 组。治疗组各组大鼠分别给予相应的药物,给药 7 d 后,行冠状动脉结扎术,结扎 30 min 后,再灌注 24 h。记录再灌注后 30 min 内心律失常发生情况,24 h 后进行血流动力学测定,然后取血进行乳酸脱氢酶(LDH)、肌酸激酶(CK)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)和过氧化氢酶(CAT)含量分析;心脏经TTC染色和HE染色,计算心肌梗死面积和心肌组织形态学观察。实时定量PCR检测SOD/GPX/CAT反应系统SOD1~SOD3、GPX1和CAT基因表达,Western blot检测细胞质和细胞核Nrf2蛋白表达。结果: 珠子参总皂苷(100、200 mg/kg)可显著降低心律失常发生率(P<0.01),能明显改善心功能,降低血液中CK、LDH含量和MDA水平,增加SOD、GSH-Px、CAT酶的活性;减轻ROS所致心肌氧化应激损伤,降低心肌梗死面积(P<0.05,P<0.01)和改善心脏组织形态学;上调SOD/GPX/CAT反应系统基因表达水平和促进Nrf2核移位,增加心肌细胞核内Nrf2的表达水平(P<0.01)。结论: 珠子参总皂苷对MI/RI具有较好的保护作用,激活Nrf2抗氧化途径和抗脂质过氧化可能是其作用机制之一。

关键词: 珠子参总皂苷, 缺血/再灌注损伤, 转录因子Nrf2, 氧化应激, 保护机制

Abstract: AIM: To investigate the cardioprotective effects of total saponin from Panacis majoris rhizoma on myocardium ischemia/reperfusion injury (MI/RI) and its mechanism.METHODS: All rats were randomly divided into four groups: sham-operated, model group and total saponin of Panacis majoris rhizoma (100, 200 mg/kg); The pretreated group was given total saponin of Panacis majoris rhizoma. After pretreating for 7 days, the myocardium ischemia model was induced by ligating the left anterior descending coronary artery in rats. After ligating 30 min, and then reperfusing 24 h. The incidence of arrhythmia at the begining 30 min, and hemodynamic parameters after 24 h were measured; The serum levels of LDH, CK, SOD, GSH-Px, CAT and MDA were also measured; Real-time PCR was applied to detect the mRNA expressions of SOD1-SOD3, GPX1 and CAT antioxidative genes, the expressions of Nrf2 in the cell hyalomitome and nucleus were detected by Western blotting.RESULTS: Total saponin from Panacis majoris rhizome (100, 200 mg/kg) might significantly decrease incidence of arrhythmia, improve heart function and heart histomorphpolgy, decrease the levels of serum LDH, CK, MDA and infarct size, improve the activities of SOD, GSH-Px, CAT (P<0.05, P<0.01, respectively); Moreover, the mRNA expressions of SOD1-SOD3, CAT and GPX1 in the myocardial tissues decreased remarkably in the model group, while were up-regulated in total saponin from Panacis majoris rhizome-pretreatment groups (P<0.05, P<0.01, respectively), the protein expressions of Nrf2 in the nucleus were significantly increased compared with model group (P<0.01, respectively), but it did not influence in the cell nucleus among the group.CONCLUSION: Total saponin from Panacis majoris rhizome exerts beneficially cardioprotective effects on MI/RI rats, mainly activating anti-oxidative pathway of Nrf2 and opposing lipid peroxidation.

Key words: Total saponin from Panacis majoris rhizome, Myocardium ischemia-reperfusion injury, Nrf2, Oxidative stress, Protection mechanism

中图分类号:

R965.2

刘爱华, 石孟琼, 杨文雁, 颜为红, 龚学谦, 熊焱强, 周继刚, 罗涛, 张继红. 珠子参总皂苷对大鼠心肌缺血/再灌注损伤的保护作用及机制研究[J]. 中国临床药理学与治疗学, 2013, 18(11): 1224-1232.

LIU Ai-hua¹, SHI Meng-qiong¹, YAN Wen-yan¹, YANG Wei-hong¹, GONG Xue-qian¹, XIONG Yan-qiang¹, ZHOU Ji-gang², LUO Tao², ZHANG Ji-hong². Cardioprotective effect and its mechanism of total saponin from Panacis majoris rhizoma on myocardium ischemia/reperfusion injury in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(11): 1224-1232.

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