Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
Int J Cardiol. 2011 Oct 20;152(2):196-201. doi: 10.1016/j.ijcard.2010.07.015. Epub 2010 Aug 6.
Dexrazoxane (DZR) is a clinically approved agent for preventive treatment of doxorubicin-induced cardiotoxicity. The objective of this study was to investigate the cardioprotective effects of DZR in a rat model of myocardial infarction (MI).
Sprague-Dawley rats were randomly divided into four groups: MI (n = 16), MI + DZR (n = 16), SHAM-operated (n = 14) and DZR-only (n = 9). MI animals were subjected to left anterior descending coronary artery ligation. DZR was administered as a single dose at 125 mg/kg intraperitoneally. Four weeks after treatment, cardiac function by echocardiography, infarct size, capillary density in the infarct border zone, bone marrow-derived endothelial progenitor cells (EPCs), and cardiac expression of Bax were measured.
Our results demonstrated that MI animals had compromised heart parameters. DZR treatment in MI animals resulted in reduction in infarct size (P = 0.013) and improved cardiac functions in terms of fractional shortening (P = 0.004) and ejection fraction (P = 0.004). The capillary density (P = 0.008) and bone marrow-derived EPCs (P < 0.05) were higher in the MI + DZR group than those in the untreated MI group. Bax expression was down-regulated in heart tissues of MI + DZR animals (P = 0.043).
Our study demonstrated that DZR exerted a cardioprotective effect in the rat model of MI, and the mechanism might be associated with anti-apoptosis and increased neovascularization.
右雷佐生(DZR)是一种临床批准的蒽环类药物心脏毒性预防治疗药物。本研究的目的是研究 DZR 在心肌梗死(MI)大鼠模型中的心脏保护作用。
将 Sprague-Dawley 大鼠随机分为四组:MI(n = 16)、MI + DZR(n = 16)、假手术(SHAM)组(n = 14)和 DZR 组(n = 9)。MI 动物接受左前降支冠状动脉结扎。DZR 以 125mg/kg 剂量单次腹腔内给药。治疗 4 周后,通过超声心动图测量心功能、梗死面积、梗死边缘区毛细血管密度、骨髓来源内皮祖细胞(EPC)和心脏 Bax 表达。
我们的结果表明,MI 动物的心脏参数受损。MI 动物给予 DZR 治疗可减少梗死面积(P = 0.013),并改善短轴缩短率(P = 0.004)和射血分数(P = 0.004)等心功能参数。MI + DZR 组的毛细血管密度(P = 0.008)和骨髓来源 EPC(P < 0.05)均高于未治疗的 MI 组。MI + DZR 动物心脏组织中 Bax 表达下调(P = 0.043)。
本研究表明,DZR 在 MI 大鼠模型中发挥了心脏保护作用,其机制可能与抗凋亡和增加新生血管形成有关。