Xanthine oxidase inhibition improves left ventricular dysfunction in dilated cardiomyopathic hamsters
Xanthine oxidase inhibition improves left ventricular dysfunction in dilated cardiomyopathic hamsters
复制标题
DOI：
10.1016/j.cardfail.2007.11.001
复制
发表时间：
2008-04-01
影响因子：
6
通讯作者：
Nagata, Kohzo
中科院分区：
文献类型：
--
作者：
Hayashi, Keiko;Kimata, Hirotaka;Nagata, Kohzo
背景：氧化应激与心脏重塑和心力衰竭有关。我们测试黄嘌呤氧化酶（XO）抑制是否可以降低心肌氧化应激和衰减左心室（LV）重塑和功能障碍的TO-2仓鼠模型dilated cardiomyosis.Methods和Results：TO-2仓鼠随机治疗XO抑制剂，别嘌呤醇，或车辆从6至12周龄。FIB仓鼠作为对照。用溶剂处理的TO-2仓鼠在6至12周之间逐渐发展为重度LV收缩功能障碍和扩张。与FIB对照组相比，这些仓鼠在12周时出现明显的心脏纤维化。在溶剂处理的TO-2仓鼠的心脏中，还原型谷胱甘肽与氧化型谷胱甘肽的比率（GSH/GSSG）降低，丙二醛水平升高。别嘌呤醇治疗6 - 12周可减轻左室功能障碍和扩张，以及心肌纤维化和胎儿型心脏基因的上调。别嘌呤醇也抑制了GSH/GSSG比值的下降和丙二醛水平的增加在heart.Conclusions：这些结果表明，慢性XO抑制别嘌呤醇减弱LV重构和功能障碍，以及心肌氧化应激在这个模型中的心力衰竭。别嘌呤醇可能被证明对心力衰竭的治疗有益。
Background: Oxidative stress is implicated in cardiac remodeling and failure. We tested whether xanthine oxidase (XO) inhibition could decrease myocardial oxidative stress and attenuate left ventricular (LV) remodeling and dysfunction in the TO-2 hamster model of dilated cardiomyopathy.Methods and Results: TO-2 hamsters were randomized to treatment with the XO inhibitor, allopurinol, or vehicle from 6 to 12 weeks of age. FIB hamsters served as controls. TO-2 hamsters treated with vehicle progressively developed severe LV systolic dysfunction and dilation between 6 and 12 weeks. Marked cardiac fibrosis was apparent in these hamsters at 12 weeks in comparison with FIB controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and malondialdehyde levels were increased in the hearts of vehicle-treated TO-2 hamsters. Treatment with allopurinol from 6 to 12 weeks attenuated LV dysfunction and dilation as well as myocardial fibrosis and the upregulation of a fetal-type cardiac gene. Allopurinol also inhibited both the decrease in GSH/GSSG ratio and the increase in malondialdehyde levels in the heart.Conclusions: These results indicate that chronic XO inhibition with allopurinol attenuates LV remodeling and dysfunction as well as myocardial oxidative stress in this model of heart failure. Allopurinol may prove beneficial for the treatment of heart failure.