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慢性呋塞米治疗的新生大鼠生长发育迟缓及骨矿物质减少

Growth failure and decreased bone mineral of newborn rats with chronic furosemide therapy.

作者信息

Koo W W, Guan Z P, Tsang R C, Laskarzewski P, Neumann V

出版信息

Pediatr Res. 1986 Jan;20(1):74-8. doi: 10.1203/00006450-198601000-00021.

DOI:10.1203/00006450-198601000-00021
PMID:3945519
Abstract

To test the hypothesis that chronic furosemide treatment in otherwise healthy newborn animals may lead to lowered bone mineral [calcium (Ca) and magnesium (Mg)] content, healthy littermates within each litter of Sprague-Dawley rat pups were randomly assigned to three groups: control, low dose furosemide (5 mg/kg/day), and high dose furosemide (15 mg/kg/day). The pups were treated between days 4 and 28 postnatally. The wet and dry weights of kidneys and tibiae significantly correlated with body weights at sacrifice. Furosemide-treated pups demonstrated a dose-dependent growth delay, decreased total bone (tibiae) Ca and Mg, increased urine Ca and Mg concentration, and a significant inverse correlation between bone Ca and urine Ca concentration. There was no significant difference among the groups when bone Ca and Mg were normalized to per gram of bone dry weight. There were no significant differences among the groups with respect to bone phosphorus or urinary phosphorus concentration; kidney and serum Ca and Mg; or serum sodium, potassium, alkaline phosphatase and immunoreactive parathyroid hormone concentration. We conclude that chronic furosemide therapy leads to growth failure and to increased urinary losses of Ca and Mg. Total bone Ca and Mg in the furosemide-treated pups were diminished in proportion to growth retardation but the bone mineral content per unit of dry weight remained similar to control pups.

摘要

为了验证在其他方面健康的新生动物中进行慢性呋塞米治疗可能会导致骨矿物质(钙和镁)含量降低这一假设,将每窝Sprague-Dawley大鼠幼崽中的健康同窝幼崽随机分为三组:对照组、低剂量呋塞米(5毫克/千克/天)组和高剂量呋塞米(15毫克/千克/天)组。在出生后第4天至28天对幼崽进行治疗。处死时,肾脏和胫骨的湿重和干重与体重显著相关。接受呋塞米治疗的幼崽表现出剂量依赖性生长延迟、总骨(胫骨)钙和镁减少、尿钙和镁浓度增加,并且骨钙与尿钙浓度之间存在显著的负相关。当将骨钙和镁按每克骨干重进行标准化时,各组之间没有显著差异。在骨磷或尿磷浓度、肾脏和血清钙和镁、或血清钠、钾、碱性磷酸酶和免疫反应性甲状旁腺激素浓度方面,各组之间没有显著差异。我们得出结论,慢性呋塞米治疗会导致生长发育迟缓以及钙和镁的尿排泄增加。接受呋塞米治疗的幼崽的总骨钙和镁与生长发育迟缓成比例减少,但每单位干重的骨矿物质含量与对照幼崽相似。

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