INDOMETHACIN AND ASPIRIN - EFFECT OF NON-STEROIDAL ANTI-INFLAMMATORY AGENTS ON THE RATE OF FRACTURE REPAIR IN THE RAT
INDOMETHACIN AND ASPIRIN - EFFECT OF NON-STEROIDAL ANTI-INFLAMMATORY AGENTS ON THE RATE OF FRACTURE REPAIR IN THE RAT
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DOI：
10.3109/17453678008990848
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发表时间：
1980-01-01
期刊：
影响因子：
--
通讯作者：
BEAR, WT
中科院分区：
文献类型：
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作者：
ALLEN, HL;WASE, A;BEAR, WT
共210只雄性Charles River CD大鼠，45日龄，在乙醚麻醉下通过手指压力使右侧桡骨和尺骨骨折。然后将这些动物随机分配至剂量组（每天1、2或4 mg/kg吲哚美辛和每天100、200或300 mg/kg阿司匹林），并给药21天。选择剂量水平以提供供试化合物的近似等效水平，最高剂量接近毒性。在第8、14和21天拍摄对照大鼠骨折的X光照片。在计划处死前，吲哚美辛剂量为4 mg/kg/天的3只大鼠死于肠穿孔。在第22天，在麻醉下通过放血处死所有剩余大鼠。在不了解治疗方案的情况下，随机检查桡骨和尺骨的组织切片。根据骨折愈合的形态学阶段进行组织学分级。与对照组相比，在所有剂量水平的吲哚美辛和最高水平的阿司匹林下，骨折愈合存在药物和剂量相关的延迟，具有统计学显著性。在每天给予100和200 mg/kg阿司匹林的组中，平均等级降低，尽管没有统计学显著性，但表明在这些水平下也对骨折愈合有延迟作用。未发现假关节数量的统计学显著变化。
A total of 210 male Charles River CD rats, 45 days old, were subjected to a fracturing of the right radius and ulna by digital pressure while under ether anesthesia. These animals were then assigned randomly to dose groups (1, 2 or 4 mg/kg per day of indomethacin and 100, 200 or 300 mg/kg per day of aspirin) and were dosed for 21 days. Dose levels were chosen to provide approximately equipotent levels of the test compounds with the highest dose approaching toxicity. Radiographs were taken of control rat fractures on days 8, 14 and 21. Three rats at 4 mg/kg per day of indomethacin died of intestinal perforation prior to scheduled sacrifice. On day 22 all remaining rats were sacrificed by exsanguination under anesthesia. Histologic sections of the radius and ulna were examined in random sequence without knowledge of the treatment regimen. A histologic grade based on the morphologic stage of fracture healing was given. There was a drug- and dose-related retardation of fracture healing, which was statistically significant at all dose levels of indomethacin and the highest level of aspirin, as compared to controls. Decreased mean grades in the groups given 100 and 200 mg/kg per day of aspirin, though not statistically significant, suggest a retarding effect on fracture healing at these levels also. No statistically significant changes in numbers of pseudoarthroses were found.