马来酸桂哌齐特对大鼠心肌损伤的保护作用

陈雪,杨涛,朱悦城,吕高阳,牛颖颖,赵丽晶

中国药学杂志 ›› 2017, Vol. 52 ›› Issue (18) : 1604-1608.

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中国药学杂志 ›› 2017, Vol. 52 ›› Issue (18) : 1604-1608. DOI: 10.11669/cpj.2017.18.010
论著

马来酸桂哌齐特对大鼠心肌损伤的保护作用

  • 陈雪a,杨涛b,朱悦城b,吕高阳b,牛颖颖b,赵丽晶a*
作者信息 +

Protection Effect of Cinepazide Maleate on Myocardial Injury in Rats

  • CHEN Xuea, YANG Taob, ZHU Yue-chengb, L Gao-yangb, NIU Ying-yingb, ZHAO Li-jinga*
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摘要

目的 探讨马来酸桂哌齐特(cinepazide maleate, CM)对异丙肾上腺素(Iso)所致大鼠心肌损伤的保护作用及其作用机制。方法 将雌雄大鼠50只分为正常组,模型组,CM低、高剂量组,卡托普利(captopril, Cap)阳性组。除正常组外,其余各组大鼠以Iso(5 mg·kg-1·d-1)皮下注射7 d建立心肌损伤模型,治疗组大鼠于造模第2天开始腹腔注射CM(1.5、3 mg·kg-1·d-1),阳性对照组大鼠灌胃给予Cap(10 mg·kg-1·d-1),正常组和模型组大鼠腹腔注射等量生理盐水,共给药14 d。各组大鼠进行3次跑步耐力测试。停药后大鼠麻醉状态下描记心电图、取血和取心,测量心重指数(HWI)及左心室重量指数(LHWI),检测心肌组织中羟脯氨酸(Hyp)含量和丙二醛(MDA)水平,血清中乳酸脱氢酶(LDH)和肌酸激酶(CK)活性及超氧化物歧化酶(SOD)活力;HE染色观察心肌组织形态学变化。结果 与正常组比较,模型组大鼠耐力值下降,心电异常,呈心律不齐或心肌缺血波形,同时HWI和LHWI增高(P<0.01),心肌组织中Hyp含量和MDA水平以及血清LDH、CK水平均增高,而血清SOD活力降低(P<0.05或P<0.01);与模型组比较,CM治疗组耐力值明显提高、心电异常现象明显改善,大鼠HWI和LHWI均降低,组织中Hyp含量、MDA水平以及血清LDH和CK水平均降低,而SOD活力增高,尤其CM高剂量组效果明显(P<0.01)。HE染色:模型组大鼠心室肌结构重塑,心肌断裂,大量胶原纤维增生,CM治疗组大鼠心室肌重构现象减轻,心肌纤维化明显改善。结论 马来酸桂哌齐特对Iso所致大鼠心肌损伤有保护作用。

Abstract

OBJECTIVE To discuss the effect and mechanism of cinepazide maleate (CM) on myocardial injured rats induced by isoproterenol (Iso). METHODS Fifty male and female rats were divided into normal group, model group, the low and the high dose group of the CM, and captopril (Cap)positive control group. The rat model of myocardial injury was established by subcutaneous injection of Iso (5 mg·kg-1·d-1)for 7 d, rats in treatment group were given intraperitoneal injection of CM on the second day (1.5,3 mg·kg-1·d-1), rats in positive control group were given intragastric administration of Cap(10 mg·kg-1·d-1), and rats in normal group and model group were given intraperitoneal injection of normal saline in the same volume, for 14 d. The rats in each group were tested before and after treatment by three times of running endurance test. After stopping drug all rats were anesthetized for measuring the electrocardiogram (ECG), then taken blood for measuring the activities of serum SOD, LDH and CK, and taken hearts for measuring heart weight index (HWI), left ventricular mass index (LHWI), the contents of myocardial hydroxyproline (Hyp)and MDA, and observing the morphological changes of myocardial tissue by HE staining. RESULTS Compared with rats in normal group, rats in model group showed endurance value decrease, ECG abnormalities (arrhythmia and myocardial ischemia in waveform), increased HWI, LHWI (P<0.01), myocardial Hyp content, myocardial MDA level, and the level of serum LDH and CK, and reduced the serum SOD activity (P<0.05 or P<0.01). Compared with model group, CM could significantly increase endurance value, improve abnormal phenomenon of ECG, lower the HWI, LHWI, myocardial Hyp content, myocardial MDA level, and serum LDH and CK levels were lower, and serum SOD activity increased, especially in high dose group of CM (P<0.01). HE staining showed in the model group rat ventricular remodeling, myocardial rupture, a large number of collagen fibers, in the treatment group, ventricular remodeling and myocardial fibrosis were significantly improved. CONCLUSION Cinepazide maleate has protective effect on myocardial injury of rats induced by Iso.

关键词

马来酸桂哌齐特 / 心肌损伤 / 超氧化物歧化酶 / 丙二醛 / 羟脯氨酸

Key words

cinepazide maleate injection / myocardial injury / superoxide dismutase / malondialdehyde / hydroxyproline

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导出引用
陈雪,杨涛,朱悦城,吕高阳,牛颖颖,赵丽晶. 马来酸桂哌齐特对大鼠心肌损伤的保护作用[J]. 中国药学杂志, 2017, 52(18): 1604-1608 https://doi.org/10.11669/cpj.2017.18.010
CHEN Xue, YANG Tao, ZHU Yue-cheng, L Gao-yang, NIU Ying-ying, ZHAO Li-jing. Protection Effect of Cinepazide Maleate on Myocardial Injury in Rats[J]. Chinese Pharmaceutical Journal, 2017, 52(18): 1604-1608 https://doi.org/10.11669/cpj.2017.18.010
中图分类号: R965   

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基金

吉林省教育厅“十二五”科学技术研究资助项目(2015396);2016年吉林省“大学生创新创业训练计划”资助项目(2016B314)
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