不同剂量异丙肾上腺素致小鼠慢性心肌缺血模型的制备及评价标准的建立
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摘要
目的颈部皮下注射不同剂量异丙肾上腺素(ISO)建立小鼠慢性心肌缺血模型,通过比较确定最佳造模剂量,寻求较为客观可靠的指标,为相关模型制备及药效评价提供参考。方法 3个模型组分别皮下注射ISO 32 mg/kg、16 mg/kg和8 mg/kg体质量,连续3 d,描记造模后24 h、8d和15 d心电图(ECG);第8天和第15天时分别检测各组血液心肌损伤标志物并心脏取材,观察各组心肌形态学病理变化。结果 ISO 32 mg/kg和ISO 16 mg/kg剂量组在造模后的8 d及15 d心电图T波均显著降低(P<0.05或P<0.01);心肌损伤标志物显著改变(P<0.05或P<0.01),其中ISO 32 mg/kg组产生病理改变,死亡率为42.5%,较适用于抗慢性心肌缺血药物较长期治疗给药的药效评价。ISO 16 mg/kg的剂量死亡率为25%,相对较低,并且未导致心肌病理性损伤。结论可根据不同试验预期选择性地采用ISO 16或32 mg/kg造模剂量建立小鼠慢性心肌缺血模型。
Objective To prepare chronic myocardial ischemia models in mice and determine the best molding dose, and to discuss the evaluation indexes of the model which could provide reference for the preparation of related models and the evaluation of their efficacy. Method Three model groups of different doses were treated with subcutaneous injection of isoproterenol(32 mg/kg, 16 mg/kg, 8 mg/kg) for three consecutive days, after 24 hours, 8 days and 15 days ECG were recorded. On the eighth day and the fifteenth day, markers of myocardial injury in the blood were detected and the morphological changes of myocardium were observed. Result The ECG, markers of myocardial injury and pathology were all markedly changed in the group of 32 mg/kg isoproterenol(P<0.05 or P<0.01), and the mortality rate was in the acceptable range. The result could be used for evaluating the efficacy of the medicine for long-term treatment of chronic myocardial ischemia.The mortality rate of the group of 16 mg/kg isoproterenol was low, and indexes of ECG and markers of myocardial injury were better than that of the group of 32 mg/kg isoproterenol, and the dose did not cause irreversible pathological damage to the heart muscle. Conclusion The result showed that the chronic myocardial ischemia models in mice can be established by using two different molding dose according to different test expectation.
Objective To prepare chronic myocardial ischemia models in mice and determine the best molding dose, and to discuss the evaluation indexes of the model which could provide reference for the preparation of related models and the evaluation of their efficacy. Method Three model groups of different doses were treated with subcutaneous injection of isoproterenol(32 mg/kg, 16 mg/kg, 8 mg/kg) for three consecutive days, after 24 hours, 8 days and 15 days ECG were recorded. On the eighth day and the fifteenth day, markers of myocardial injury in the blood were detected and the morphological changes of myocardium were observed. Result The ECG, markers of myocardial injury and pathology were all markedly changed in the group of 32 mg/kg isoproterenol(P<0.05 or P<0.01), and the mortality rate was in the acceptable range. The result could be used for evaluating the efficacy of the medicine for long-term treatment of chronic myocardial ischemia.The mortality rate of the group of 16 mg/kg isoproterenol was low, and indexes of ECG and markers of myocardial injury were better than that of the group of 32 mg/kg isoproterenol, and the dose did not cause irreversible pathological damage to the heart muscle. Conclusion The result showed that the chronic myocardial ischemia models in mice can be established by using two different molding dose according to different test expectation.
引文
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[9] 石孟琼,白彩虹,孙桂林,等.开口箭不同提取部位对异丙肾上腺素致小鼠心肌缺血损伤的影响[J].中国临床药理学与治疗学,2013,18(12):1344-1352.
[10] 余保瑞,龙超良,夏云峰,等.哌芳安他对异丙肾上腺素诱发的小鼠心肌缺血的保护作用[J].中国临床药理学与治疗学,2004,(6):637-640.
[11] 王治宝,杨辉,闫早婴,等.蒙古口蘑水提物对异丙肾上腺素致心肌缺血小鼠的心肌保护作用[J].食用菌学报,2014,21(1):47-50.
[12] 王宇卿,朱丹妮,张洁琼,等.生脉冻干粉口服对异丙肾上腺素致小鼠心肌缺血损伤的保护作用[J].中药药理与临床,2013,29(3):15-17.
[13] 吕建英.曲马多对异丙肾上腺素所致小鼠心肌缺血损伤的抑制作用[J].华北煤炭医学院学报,2010,12(5):609-610.
[14] 范英兰,胡丽萍,朱竟赫,等.心肌缺血动物模型实验研究进展[J].实验动物科学,2018,35(1):72-75.
[15] 牛子冉, 徐晓娜, 陈俞材, 等. 丹酚酸A对异丙肾上腺素致小鼠心肌缺血的保护作用及其机制[J]. 中国药理学通报, 2015,(12):1667-1674.
[16] 冷雪, 贾连群, 王莹,等. 人参皂苷素Rb1预处理对异丙肾上腺素诱导大鼠急性心肌缺血心肌凋亡相关蛋白表达的影响[J]. 辽宁中医杂志, 2017,(1):184-186.
[17] 雷健, 陶光利. 血脉灵组方对急性心肌缺血大鼠的保护[J]. 医药导报, 2017, 36(12):1359-1362.
[18] 吴阿兰, 苏伟青, 胡荣权,等. 心肌梗死及其预后与心肌酶谱、红细胞参数的相关性研究[J]. 临床医学工程, 2017, 24(1):75-76.
[19] 胡娟娟, 郝晓柯, 周铁城,等. 心肌损伤标志物联合检测在急性心肌梗死早期诊断中的应用价值[J]. 国际检验医学杂志, 2017, 38(11):1545-1547.
[2] 焦淑萍, 周玮, 杜培革. 野生山葡萄多酚对异丙肾上腺素诱发的小鼠心肌缺血的保护作用[J]. 中国地方病防治杂志, 2006, 21(3):146-147.
[3] Ribeiro D A,Buttros J B,Oshima C T,et al.Ascorbic acid prevents acutemy ocardial infarction induced by isoproterenol in rats:role of induciblenitric oxide synthase production[J].MolHistol,2009,40(2):99-105.
[4] Prabhu S,Narayan S,Devi C S.Mechanism of protective action of mangiferin on suppression of inflammatory response and lysosomal instability in ratmodel of myocardial infarction[J].PhytotherRes,2009,23(6):756-760.
[5] Kubavat J B,Asdaq S M. Role of Sida cordifolia L leaves on biochemical and antioxidant profile during myocardial injury[J].Ethnopharmacol,2009,124(1):162-165.
[6] 修春江,刘风岐,王怀泉,等.组织多普勒超声评价交感神经阻滞对扩张型心肌病左心室心肌收缩力的影响[J].中华超声影像学杂志,2005,14(5):338-341.
[7] 徐叔云. 药理学实验方法[M]. 第 2 版.北京: 人民卫生出版社, 1991:897.
[8] 常厦云,朱凌鹏,王秋娟,等.红景天苷对异丙肾上腺素诱导的小鼠心肌缺血的影响[J].中药药理与临床,2016,32(2):67-70.
[9] 石孟琼,白彩虹,孙桂林,等.开口箭不同提取部位对异丙肾上腺素致小鼠心肌缺血损伤的影响[J].中国临床药理学与治疗学,2013,18(12):1344-1352.
[10] 余保瑞,龙超良,夏云峰,等.哌芳安他对异丙肾上腺素诱发的小鼠心肌缺血的保护作用[J].中国临床药理学与治疗学,2004,(6):637-640.
[11] 王治宝,杨辉,闫早婴,等.蒙古口蘑水提物对异丙肾上腺素致心肌缺血小鼠的心肌保护作用[J].食用菌学报,2014,21(1):47-50.
[12] 王宇卿,朱丹妮,张洁琼,等.生脉冻干粉口服对异丙肾上腺素致小鼠心肌缺血损伤的保护作用[J].中药药理与临床,2013,29(3):15-17.
[13] 吕建英.曲马多对异丙肾上腺素所致小鼠心肌缺血损伤的抑制作用[J].华北煤炭医学院学报,2010,12(5):609-610.
[14] 范英兰,胡丽萍,朱竟赫,等.心肌缺血动物模型实验研究进展[J].实验动物科学,2018,35(1):72-75.
[15] 牛子冉, 徐晓娜, 陈俞材, 等. 丹酚酸A对异丙肾上腺素致小鼠心肌缺血的保护作用及其机制[J]. 中国药理学通报, 2015,(12):1667-1674.
[16] 冷雪, 贾连群, 王莹,等. 人参皂苷素Rb1预处理对异丙肾上腺素诱导大鼠急性心肌缺血心肌凋亡相关蛋白表达的影响[J]. 辽宁中医杂志, 2017,(1):184-186.
[17] 雷健, 陶光利. 血脉灵组方对急性心肌缺血大鼠的保护[J]. 医药导报, 2017, 36(12):1359-1362.
[18] 吴阿兰, 苏伟青, 胡荣权,等. 心肌梗死及其预后与心肌酶谱、红细胞参数的相关性研究[J]. 临床医学工程, 2017, 24(1):75-76.
[19] 胡娟娟, 郝晓柯, 周铁城,等. 心肌损伤标志物联合检测在急性心肌梗死早期诊断中的应用价值[J]. 国际检验医学杂志, 2017, 38(11):1545-1547.