Xiao Jun, She Qiang, Wang Yang, Luo Kailiang, Yin Yuehui, Hu Rong, Huang Kaishun
Department of Cardiology, The Second Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing 400010, China.
Eur J Heart Fail. 2009 Jan;11(1):20-7. doi: 10.1093/eurjhf/hfn003.
This study was designed to explore the effect of the xanthine oxidase (XO) inhibitor allopurinol on cardiomyocyte apoptosis after myocardial infarction (MI) in a rat model.
MI was induced in rats by ligation of the anterior descending coronary artery. Survivors were randomly divided into three groups: sham operation group, MI group, and allopurinol group (50 mg kg(-1) day(-1)). After 28 days, infarction size was measured. In non-infarcted zones (NIZ), apoptosis index (AI) was measured by TUNEL [terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-conjugated dUTP nick-end labelling]; expression of Fas was detected by immunohistochemistry, and expression of XO and Caspase-3 by western blot. In addition, XO and O(2)(-), OH-scavenging activity of myocardial tissue in the NIZ were measured by colorimetry. Results suggest that AI and expression of Fas and Caspase-3 in the NIZ were significantly depressed in the allopurinol group, compared with MI group; moreover, activity of XO was significantly decreased while O(2)(-) and OH-scavenging activity were significantly increased in the allopurinol group. Ventricular remodelling was attenuated but there were no significant differences in infarct size or XO expression levels between the allopurinol and MI groups.
Our results suggest that allopurinol may inhibit cardiomyocyte apoptosis in the NIZ in rats. The potential mechanism could be related to its ability to reduce reactive oxygen species and to depress the expression of Fas and Caspase-3.
本研究旨在探讨黄嘌呤氧化酶（XO）抑制剂别嘌醇对大鼠心肌梗死（MI）后心肌细胞凋亡的影响。
通过结扎冠状动脉前降支诱导大鼠发生MI。存活的大鼠随机分为三组：假手术组、MI组和别嘌醇组（50mg/kg·d-1）。28天后，测量梗死面积。在非梗死区（NIZ），采用末端脱氧核苷酸转移酶介导的地高辛标记法（TUNEL）检测凋亡指数（AI）；采用免疫组织化学法检测Fas的表达，采用蛋白质印迹法检测XO和半胱天冬酶-3的表达。此外，采用比色法测定NIZ心肌组织中XO以及超氧阴离子（O2-）、羟自由基（OH）清除活性。结果显示，与MI组相比，别嘌醇组NIZ中的AI、Fas和半胱天冬酶-3的表达明显降低；此外，别嘌醇组XO活性明显降低，而O2-和OH清除活性明显增加。心室重构得到减轻，但别嘌醇组与MI组之间梗死面积或XO表达水平无显著差异。
我们的结果表明，别嘌醇可能抑制大鼠NIZ中的心肌细胞凋亡。潜在机制可能与其降低活性氧以及抑制Fas和半胱天冬酶-3表达的能力有关。
