Impact of elevated uric acid on ventricular remodeling in infarcted rats with experimental hyperuricemia
Impact of elevated uric acid on ventricular remodeling in infarcted rats with experimental hyperuricemia
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DOI：
10.1152/ajpheart.01071.2010
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发表时间：
2011-09-01
影响因子：
4.8
通讯作者：
Lee, Tsung-Ming
中科院分区：
文献类型：
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作者：
Chen, Chien-Chang;Hsu, Yu-Jung;Lee, Tsung-Ming
陈昌昌，徐玉君，李德铭。尿酸升高对实验性高尿酸血症梗死大鼠心室重构的影响。Am J Physiol Heart Circ Physiol 301：H1107-H1117，2011.首次发表于2011年5月27日; doi：10.1152/ajpheart.01071.2010.-高尿酸血症与心血管疾病有关，但它通常被认为是一个标志物，而不是一个危险因素。以往在正常尿酸血症动物中使用降尿酸药物的研究不适合回答高尿酸血症对心肌梗死后心室重构的影响。本研究的目的是确定高尿酸血症是否对尿酸升高的梗死大鼠心室重构产生不利影响。将8周龄雄性Wistar大鼠随机分为溶剂组、oxonic acid组、oxonic acid +别嘌呤醇组、oxonic acid +苯溴马隆组、oxonic acid + ABT-627组或oxonic acid + tempol组，结扎后24 h开始给药4周。心肌梗死后与氧化剂产生增加相关，通过心肌超氧化物、异前列腺素、黄嘌呤氧化酶活性和二氢乙锭染色进行测量。与正常尿酸血症梗死大鼠相比，高尿酸血症梗死大鼠的超氧化物产生（1.7倍）和内皮素-1蛋白（1.2倍）和mRNA（1.4倍）表达显著增加，这与左室功能障碍增加，心肌肥厚和纤维化增加有关。这些变化都可以通过别嘌呤醇治疗来预防。对于相似水平的尿酸盐降低，促尿酸排泄剂苯溴马隆对心室重构没有影响。尽管有相同的高尿酸血症，但ABT-627和tempol减弱心室重构的能力表明内皮素-1和氧化还原途径的参与。高尿酸血症可能通过超氧化物和内皮素-1依赖性途径与不利的心室重构相关。在不抑制超氧化物和内皮素-1的情况下降低尿酸可能对重塑没有影响。长期服用别嘌呤醇、ABT-627和Tempol与心室重塑减弱相关。
Chen CC, Hsu YJ, Lee TM. Impact of elevated uric acid on ventricular remodeling in infarcted rats with experimental hyperuricemia. Am J Physiol Heart Circ Physiol 301: H1107-H1117, 2011. First published May 27, 2011; doi:10.1152/ajpheart.01071.2010.-Hyperuricemia is associated with cardiovascular disease, but it is usually considered a marker rather than a risk factor. Previous studies using uric acid-lowering drugs in normouricemic animals are not suitable to answer the effect of hyperuricemia on ventricular remodeling after myocardial infarction. The purpose of this study was to determine whether hyperuricemia adversely affects ventricular remodeling in infarcted rats with elevated uric acid. Male Wistar rats aged 8 wk were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, oxonic acid + ABT-627, or oxonic acid + tempol for 4 wk starting 24 h after ligation. Postinfarction was associated with increased oxidant production, as measured by myocardial superoxide, isoprostane, xanthine oxidase activity, and dihydroethidium staining. Compared with normouricemic infarcted rats, hyperuricemic infarcted rats had a significant increase of superoxide production (1.7X) and endothelin-1 protein (1.2X) and mRNA (1.4X) expression, which was associated with increased left ventricular dysfunction and enhanced myocardial hypertrophy and fibrosis. These changes were all prevented by treatment with allopurinol. For similar levels of urate lowering, the uricosuric agent benzbromarone had no effect on ventricular remodeling. In spite of equivalent hyperuricemia, the ability of both ABT-627 and tempol to attenuate ventricular remodeling suggested involvement of endothelin-1 and redox pathways. Hyperuricemia is associated with unfavorable ventricular remodeling probably through a superoxide and endothelin-1-dependent pathway. Uric acid lowering without inhibition of superoxide and endothelin-1 may not have an effect on remodeling. Chronic administration of allopurinol, ABT-627, and tempol is associated with attenuated ventricular remodeling.