[1]王亦如,蔡新华.盐酸异丙肾上腺素腹腔注射建立心肌缺血性坏死大鼠模型的最佳药物浓度研究[J].新乡医学院学报,2019,36(10):922-926.[doi:10.7683/xxyxyxb.2019.10.005]
　WANG Yi-ru,CAI Xin-hua.Optimum concentration of isoprenaline hydrochloride in establishing the rat model of myocardial ischemic necrosis[J].Journal of Xinxiang Medical University,2019,36(10):922-926.[doi:10.7683/xxyxyxb.2019.10.005]
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盐酸异丙肾上腺素腹腔注射建立心肌缺血性坏死大鼠模型的最佳药物浓度研究
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
36
期数:
2019年10
页码:
922-926
栏目:
基础研究
出版日期:
2019-10-05

文章信息/Info

Title:
Optimum concentration of isoprenaline hydrochloride in establishing the rat model of myocardial ischemic necrosis
作者:
王亦如1; 蔡新华2
(1.广西医科大学附属肿瘤医院妇瘤科暨区域性高发肿瘤早期防治研究教育部重点实验室，广西　南宁　530000；2.新乡医学院基础医学院组织胚胎学教研室，河南　新乡　453003)
Author(s):
WANG Yi-ru1; CAI Xin-hua2
(1.Department of Gynecological Oncology,Guangxi Medical University Affiliated Tumor Hospital,Key Laboratory for Early Prevention and Treatment of Endemic High Incidence of Tumor,Ministry of Education,Nanning 530000,Guangxi Province，China；2.Department of Histology and Embryology,School of Basic Medical Sciences,Xinxiang Medical University,Xinxiang　453003,Henan Province,China)
关键词:
盐酸异丙肾上腺素; 心肌缺血性坏死; 形态学; 血清学; 大鼠模型
Keywords:
isoprenaline hydrochloride; myocardial ischemic necrosis; morphology; serology; rat model
分类号:
R542.2
DOI:
10.7683/xxyxyxb.2019.10.005
文献标志码:
A
摘要:
目的　探讨盐酸异丙肾上腺素（ISO）诱导心肌缺血性坏死动物模型的最佳药物浓度。方法　将42只健康雄性Sprague Dawley大鼠随机分为对照组和2、4、6、8、10 mg·kg-1ISO组，每组7只。2、4、6、8、10 mg·kg-1ISO组大鼠分别按照2、4、6、8、10 mg·kg-1将ISO配成10 mL工作液进行腹腔注射，对照组大鼠给予同体积生理盐水腹腔注射，每日1次，连续7 d。每日注射后15 min及第8天麻醉大鼠稳定后监测各组大鼠心电图；腹腔注射结束的第2天开胸取心室血检测各组大鼠血清肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）、天门冬氨酸氨基转移酶（AST）和ɑ-羟丁酸脱氢酶（ɑ-HBDH）水平，以辅助判断大鼠心肌缺血性坏死程度；取左心室心肌组织制备切片，苏木精-伊红染色，利用Image J图像分析软件分析心肌缺血坏死区面积百分比。结果　ISO腹腔注射第7天，对照组大鼠心电图表现正常，2、4、6、8、10 mg·kg-1ISO组大鼠心电图均可见心肌缺血性改变。2、4 mg·kg-1ISO组大鼠心率高于对照组（P<0.05），8、10 mg·kg-1ISO组大鼠心率低于对照组（P<0.05）；6 mg·kg-1ISO组大鼠心率与对照组比较差异无统计学意义（P>0.05）；其中，4 mg·kg-1ISO 组大鼠心率加快，其心电图ST段呈弓背向上抬高，出现病理性Ｑ波。 与对照组比较，4、6、8、10 mg·kg-1ISO组大鼠血清AST、LDH、ɑ-HBDH显著升高（P<0.05），2、4、6、8、10 mg·kg-1 ISO组大鼠血清CK、CK-MB显著升高（P<0.05）。与2 mg·kg-1ISO组比较，4、6、8、10 mg·kg-1ISO组大鼠血清AST、CK、CK-MB显著升高（P<0.05），6、8、10 mg·kg-1ISO组大鼠血清LDH显著升高（P<0.05），8、10 mg·kg-1ISO组大鼠血清ɑ-HBDH显著升高（P<0.05）。与4 mg·kg-1ISO组比较， 6、8 mg·kg-1ISO组大鼠血清CK显著升高（P<0.05），8 mg·kg-1ISO组大鼠血清CK-MB显著升高（P<0.05）。与6 mg·kg-1ISO组比较，10 mg·kg-1ISO组大鼠血清CK显著降低（P<0.05），8 mg·kg-1 ISO组大鼠血清CK-MB显著升高（P<0.05）。与8 mg·kg-1ISO组比较， 10 mg·kg-1ISO组大鼠血清CK、CK-MB显著降低（P<0.05）。心肌组织病理学结果显示，ISO不同剂量组大鼠均出现心室肌细胞缺血坏死，4、6、8、10 mg·kg-1ISO组大鼠心肌缺血坏死区面积均大于2 mg·kg-1ISO组（P<0.05），其余组间两两比较差异无统计学意义（P>0.05）。结论　不同剂量ISO腹腔注射均可造成大鼠心肌缺血坏死性损伤，但4 mg·kg-1ISO腹腔注射制备心肌缺血性坏死大鼠模型的效果最佳。
Abstract:
Objective　 To explore the optimum drug concentration of isoprenaline hydrochloride（ISO） in establishing the rat model of myocardial ischemic necrosis.Methods　Forty-two healthy male Sprague Dawley rats were randomly divided into control group and 2，4，6，8 and 10 mg·kg-1 ISO group，with 7 rats in each group.The rats in 2，4，6，8，10 mg·kg-1 ISO group were intraperitoneally injected with 10 mL working fluid which was compounded according to the dose of 2，4，6，8 and 10 mg·kg-1 ISO respectively.The rats in the control group were given the same volume of saline by intraperitoneal injection,once a day for 7 days.The electrocardiogram(ECG) of rats in each group was monitored at 15 minutes after intraperitoneal injection and before sampling.On the 2nd day after intraperitoneal injection，the ventricular blood of rats was taken by opening the chest and the levels of creatine kinase (CK)，creatine kinase isoenzyme (CK-MB)，lactate dehydrogenase (LDH)，aspartate aminotransferase (AST) and ɑ-hydroxybutyrate dehydrogenase (ɑ-HBDH) were detected to help determining the degree of myocardial ischemic necrosis of rats.Myocardial tissue sections were prepared and stained with hematoxylin-eosin.The percentage of myocardial ischemic necrosis area was analyzed by Image J image analysis software.Results　The ECG of the rats in the control group was normal,and the changes of myocardial ischemia were observed in the 2，4，6，8,10 mg·kg-1 ISO group.The hear rates of rats in 2,4 mg·kg-1 ISO group were higher than those in the control group（P<0.05），while the heart rate of rats in 8 ,10 mg·kg-1 ISO group were lower than that in the control group（P<0.05）; there was no statistic difference in the heart rate of rats between the 6 mg·kg-1 ISO group and the control group （P>0.05）.The heart rate of rats in 4 mg·kg-1 ISO group increased，and the ST segment of ECG showed arch-back upward elevation，and the pathological Q wave appeared.Compared with the control group, the serum level of AST、LDH、ɑ-HBDH of rats in the 4,6,8,10 mg·kg-1 ISO group increased significantly （P<0.05）;the serum levels of CK and CK-MB of rats in the 2,4, 6, 8,10 mg·kg-1 ISO group increased significantly（P<0.05）.Compared with the 2 mg·kg-1 ISO group, the serum levels of AST 、CK、CK-MB of rats in the 4,6,8,10 mg·kg-1 ISO group increased significantly（P<0.05）; the serum level of LDH of rats in the 6, 8,10 mg·kg-1 ISO group increased significantly（P<0.05）; the serum level of ɑ-HBDH of rats in the 8,10 mg·kg-1 ISO group increased significantly（P<0.05）.Compared with the 4 mg·kg-1 ISO group, the serum level of CK of rats in the 6,8 mg·kg-1 ISO group increased significantly （P<0.05）; the serum level of CK-MB of rats in the 8 mg·kg-1 ISO group increased significantly （P<0.05）.Compared with the 6 mg·kg-1 ISO group, the serum level of CK of rats in the 10 mg·kg-1 ISO group decreased significantly（P<0.05）;the serum level of CK-MB of rats in the 8 mg·kg-1 ISO group increased significantly （P<0.05）.Compared with the 8 mg·kg-1 ISO group, the serum level of CK、CK-MB of rats in the 10 mg·kg-1 ISO group decreased significantly（P<0.05）.Histopathological observation of myocardium showed that ischemic necrosis of ventricular myocytes occurred in rats of different doses of ISO.The area of myocardial ischemic necrosis of rats in the 4，6，8,10 mg·kg-1 ISO group was larger than that in the 2 mg·kg-1 ISO group（P<0.05）;there was no significant difference in the area of myocardial ischemic necrosis of rats between the other groups (P>0.05).Conclusion　Different doses of ISO can lead to myocardial ischemia and necrosis injury in rats，and 4 mg·kg-1 ISO is the best dose in establishing the rat model of myocardial ischemic necrosis.

参考文献/References:

［1］　孔艳,李玉泉,杨向群.脂肪来源干细胞治疗心肌梗死的现状及策略［J］.中华细胞与干细胞杂志：电子版,2019,9(1):40-43.DOI:10.3877/cma.j.issn.2095-1221.2019.01.008.
［2］　陆小华,张璐,文建霞，等.心力衰竭大鼠模型的研究进展［J］.中国医院用药评价与分析,2018,18(11):1444-1446，1449.
［3］　闫阳,姚禹,陈起帆.药物致心肌损伤的方法举例与评估［J］.临床医药文献电子杂志,2017,4(31):6125-6126.DOI：10.16281/j.cnki.jocml.2017.31.150.
［4］　赵美眯,李卓,杨艳,等.注射异丙肾上腺素建立大鼠心肌肥厚模型［J］.中国医科大学学报,2017,46(5):406-408，412.
［5］　陶宁亚,张贝,任阳光,等.急性心肌梗死检测方法的研究进展［J］.东南大学学报(医学版),2018,37(6):1085-1088.
［6］　张卫强,王涛,张志明,等.大鼠心肌缺血再灌注损伤模型的改进与评判［J］.中国实验动物学报,2018,26(3):311-316.
［7］　张东,贾连群,杨关林,等.急慢性心肌缺血动物模型造模方法研究简况［J］.实用中医内科杂志,2018,32(5):75-77.
［8］　杨梦思,汤圣兴.骨髓相关蛋白在异丙肾上腺素制作的大鼠心肌损伤坏死模型中的诊断价值［J］.临床心血管病杂志,2014,30(5):436-439.
［9］　VARIYA B C,PATEL S S,TRIVEDI J I,et al.Comparative evaluation of HMG CoA reductase inhibitors in experimentally-induced myocardial necrosis: biochemical,morphological and histological studies［J］.Eur J Pharmacol,2015,764:283-291.
［10］　MD HASSAN Q,AKHTAR M,AHMED S,et al.Nigella sativa protects against isoproterenol-induced myocardial infarction by alleviating oxidative stress,biochemical alterations and histological damage［J］.Asian Pac J Trop Med,2017,7(4):294-299.
［11］　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.
［12］　梁娟,刘越,尹新华.异丙肾上腺素所致心肌损伤动物模型的研究进展［J］.中国实验动物学报,2019,27(1):110-114.
［13］　戴有金,付鹤玲,鲍丹,等.CD47抗体对异丙肾上腺素诱导的大鼠心肌细胞损伤的保护作用［J］.中国医药导报，2018,15(26):13-17，21.
［14］　高东雁,刘健,李卫平，等.山楂叶总黄酮对大鼠心肌缺血性损伤的保护作用及机制研究［J］.中药药理与临床,2012,28(5):64-66.

更新日期/Last Update: 2019-10-05