Enhanced gene expression of myocardial matrix metalloproteinases 2 and 9 after acute treatment with doxorubicin in mice
Enhanced gene expression of myocardial matrix metalloproteinases 2 and 9 after acute treatment with doxorubicin in mice
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DOI：
10.1016/j.phrs.2006.01.001
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发表时间：
2006-04-01
影响因子：
9.3
通讯作者：
Hara, Y
中科院分区：
文献类型：
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作者：
Kizaki, K;Ito, R;Hara, Y
我们研究了单次剂量为25 mg kg（-1）的阿霉素（DOX）急性处理诱导小鼠心肌病后1、2和4天心室中基质金属蛋白酶（MMP）-2和MMP-9基因的表达。心室重量、心室重量-尾长比、左心室收缩期和舒张期内径均呈时间依赖性下降。组织学显示，与对照组相比，第4天DOX治疗小鼠的心肌细胞空泡化增加。北方印迹杂交显示，MMP-2和MMP-9基因转录增加，在心室的阿霉素治疗的小鼠在第2天。MMP-2 mRNA在DOX处理的小鼠中在第1天和第2天大约加倍，使用定量实时逆转录聚合酶链反应测量。相比之下，MMP-9 mRNA表达在第1天在两组中没有差异，而在第2天和第4天在DOX处理的小鼠中分别显著增加至2.9倍和2.1倍。因此，MMP-2和MMP-9的基因表达诱导后，与DOX治疗的心室，表明他们可能发挥了重要作用，在DOX诱导的心脏毒性的发展。(c)2006爱思唯尔有限公司保留所有权利。
We investigated the expression of the genes for matrix metalloproteinases (MMP)-2 and MMP-9 in the ventricle for 1, 2 and 4 days after acute treatment with doxorubicin (DOX) to induce cardiomyopathy in mice, at a single dose of 25 mg kg(-1). Ventricle weights, ventricle weight-to-tail length ratios, and left ventricular systolic and diastolic internal dimensions all decreased time-dependently. Histology showed increased vacuolisation of cardiomyocytes in the DOX-treated mice on day 4 compared with controls. Northern blot hybridisation revealed that MMP-2 and MMP-9 gene transcripts increased in the ventricle of DOX-treated mice on day 2. MMP-2 mRNA approximately doubled in the DOX-treated mice on days 1 and 2, measured using quantitative real-time reverse transcription polymerase chain reaction. By contrast, MMP-9 mRNA expression did not differ in either group on day 1, whereas it increased significantly to 2.9-fold and 2.1-fold in the DOX-treated mice on days 2 and 4, respectively. Consequently, MMP-2 and MMP-9 gene expressions are induced in the ventricle after treatment with DOX, indicating that they might play an important role in the development of DOX-induced cardiotoxicity. (c) 2006 Elsevier Ltd. All rights reserved.