Int J Cardiol 2011 Oct;152 (2): 196-201. [IF:6.802]
Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction:
anti-apoptosis and promoting angiogenesis.
Zhou L , Sung RY , Li K , Pong NH , Xiang P , Shen J , Ng PC , Chen Y .
Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
重庆医科大学儿童医院心内科
Abstract
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.
摘要：
右雷佐生是一种在预防阿霉素引发的心脏毒性的非常有效的药。这项研究的目的是调查右雷佐生在大鼠心肌梗死模型的保护作用。Sprague-Dawley鼠随机分为四组：心肌梗死(n = 16),心肌梗死 + 右雷佐生 (n = 16), 假手术组 (n = 14) and 右雷佐生(n = 9).通过结扎左前降冠脉制造心肌梗死模型。右雷佐生腹腔给予剂量为125 mg/kg。四周治疗之后，测量超声心动图、梗死面积、梗死边缘区毛细血管密度、骨髓内皮原始细胞及心脏bax表达。结果表明，心肌梗死组有明显的心脏受损。在心肌梗塞+右雷佐生组梗塞面积减少(P = 0.013)，通过缩短射血分数(P=0.004、P=0.004)改善心机功能。在心肌梗塞+右雷佐生组，毛细血管密度(P=0.008)和骨髓衍生EPCs (P<0.05)比那些未经治疗的心肌梗组要高。Bax表达在心肌梗死+右雷佐生组心肌组织中明显降低(P = 0.043).这一研究说明右雷佐生在大鼠M1模型中具有心脏保护作用，其机制可能与抗吞噬和促进新生血管形成有关。
