Protective effects of dantrolene against myocardial injury induced by isoproterenol in rats: Biochemical and histological findings
Protective effects of dantrolene against myocardial injury induced by isoproterenol in rats: Biochemical and histological findings
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DOI：
10.1016/j.ijcard.2003.10.054
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发表时间：
2005-02-28
影响因子：
3.5
通讯作者：
Senocak, H
中科院分区：
文献类型：
--
作者：
Acikel, M;Buyukokuroglu, ME;Senocak, H
目的：我们使用大鼠实验模型研究丹曲林是否可以保护心脏免受异丙肾上腺素（ISO）诱导的心肌损伤（MI）。研究方法：将28只大鼠随机分为对照组（n = 8）、ISO组（n = 8）、低剂量丹曲林（LDD）+ ISO组（LDD组，n = 6）和高剂量丹曲林（HDD）+ ISO组（HDD组，n = 6）。ISO（150 mg/kg/天，皮下注射），LDD（5 mg/kg/天，i.p.）和HDD（10 mg/kg/天，i. p.）每天一次，连续两天。在第二天结束时，在麻醉大鼠后不久从腹主动脉采集血液样品用于心肌肌钙蛋白T（cTnT）和I（cTnI）测定，并取出心脏并在显微镜下观察。结果：与对照组相比，ISO组的cTnT和cTnI水平升高（p < 0.001）。与ISO组相比，LDD和HDD显著降低cTnT和cTnI水平。cTnT和cTnI的升高似乎与组织学变化的严重程度有关。ISO组中表现出显著MI的动物比率高于对照组（p < 0.001）。LDD组和HDD组大鼠的组织学变化均小于ISO组（p < 0.01）。对照组与LDD和HDD组之间无显著差异。结论：本研究表明丹曲林对ISO诱导的心肌梗死具有显著的保护作用。我们认为，预处理丹曲林可能有助于开发新的战略，在心脏毒性动物模型和预防的心脏毒性作用的水平升高的儿茶酚胺。(c)2004爱思唯尔爱尔兰有限公司保留所有权利。
Purpose: We investigated whether dantrolene might protect the heart against myocardial injury (MI) induced by isoproterenol (ISO), using an experimental model in rats. Methods: Twenty-eight rats were randomized to treatment with saline only (control group, n = 8), ISO only (ISO group, n = 8), low-dose dantrolene (LDD) + ISO (LDD group, n = 6) and high-dose dantrolene (HDD) + ISO (HDD group, n = 6). ISO (150 mg/kg/day, s.c.), LDD (5 mg/kg/day, i.p.) and HDD (10 mg/kg/day, i.p.) were given once a day for two consecutive days. At the end of the second day, blood samples were taken from abdominal aorta shortly after the rats were anesthetised for cardiac troponins T (cTnT) and I (cTnI) assay, and the hearts were removed and observed microscopically. Results: cTnT and cTnI levels were increased in the ISO group when compared with the control group (p < 0.001). LDD and HDD significantly reduced cTnT and cTnI levels when compared with the ISO group. Elevations of cTnT and cTnI appeared to relate to the severity of histological changes. The rate of animals that exhibited marked MI was higher in the ISO group than in the control group (p < 0.001). The rats in both LDD and HDD groups showed less histological changes when compared to the ISO group (p < 0.01). There was no significant difference between the control group and both LDD and HDD groups. Conclusions: This study shows that dantrolene has a significant effect in the protection of the heart against MI induced by ISO. We believe that pretreatment with dantrolene may contribute to developing novel strategies in the cardiotoxicity animal models and in the prevention of the cardiotoxic effects of elevated levels of catecholamines. (c) 2004 Elsevier Ireland Ltd. All rights reserved.