Wang Zhenzhen, Ding Juan, Luo Xiang, Zhang Siliang, Yang Gang, Zhu Que, Liu Dichuan
Department of Cardiology, Second Affiliated Hospital, Chongqing Medical University.
Int Heart J. 2016 Dec 2;57(6):753-759. doi: 10.1536/ihj.16-149. Epub 2016 Nov 4.
To determine the effect of the xanthine oxidase (XO) inhibitor allopurinol on myocardial energy metabolism in a chronic heart failure rat model after myocardial infarct.An AMI model was established in 6-week-old rats via the ligation of the anterior descending coronary artery. Thirty-five rats were randomly divided into the following 3 groups: an ALLO group, an AMI group, and a Sham group. Heart failure was successfully diagnosed via echocardiography and blood tests. Xanthine oxidase (XO), malondialdehyde (MDA), PGC-1α, CPT-1, and GLUT4 were monitored in the myocardium.The TEM results demonstrated that myofilament lysis and mitochondrial swelling were alleviated in the ALLO group compared with the AMI group (without ALLO). The results also demonstrated that cardiac function was significantly improved in the ALLO group compared with the AMI group. Compared with the AMI group, the ALLO group exhibited increased respiratory-chain enzyme activity, as well as increased PGC-1α and CPT-1 mRNA and protein expression, decreased MDA content, and decreased XO and GLUT4 mRNA and protein expression.ALLO improves myocardial energy metabolism in rats with chronic heart failure, which may result from the regulation of PGC-1α in the setting of glycolipid metabolism, enhancing the production of ATP.
为了确定黄嘌呤氧化酶(XO)抑制剂别嘌呤醇对心肌梗死后慢性心力衰竭大鼠模型心肌能量代谢的影响。通过结扎6周龄大鼠的冠状动脉前降支建立急性心肌梗死(AMI)模型。35只大鼠随机分为以下3组:别嘌呤醇组(ALLO组)、AMI组和假手术组。通过超声心动图和血液检测成功诊断心力衰竭。监测心肌中的黄嘌呤氧化酶(XO)、丙二醛(MDA)、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)、肉碱棕榈酰转移酶-1(CPT-1)和葡萄糖转运蛋白4(GLUT4)。透射电镜结果表明,与AMI组(无别嘌呤醇)相比,ALLO组的肌丝溶解和线粒体肿胀减轻。结果还表明,与AMI组相比,ALLO组的心功能显著改善。与AMI组相比,ALLO组的呼吸链酶活性增加,PGC-1α和CPT-1的mRNA和蛋白表达增加,MDA含量降低,XO和GLUT4的mRNA和蛋白表达降低。别嘌呤醇改善慢性心力衰竭大鼠的心肌能量代谢,这可能是由于在糖脂代谢过程中对PGC-1α的调节,增强了三磷酸腺苷(ATP)的产生。