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Case Report: High Mortality Associated with Ketorolac Treatment in CByB6F1 Mice after Embryo Transfer Surgery

病例報告:Ketorolac增加胚移置手術後CByB6F1小鼠的死亡率

摘要


Ketorolac是一非固醇類消炎藥(NSAID),在人類與囓齒類動物常做為術後止痛劑。在國家實驗動物中心例行性胚移置手術(ET)中,我們發現使用ketorolac (4.0mg/kg SC)於假懷孕CByB6F1母鼠的術後止痛,與使用ketoprofen (3.3mg/kg SC)的組別比較,會顯著增加母鼠術後1-2天內的死亡率(29% [49隻死亡14隻]vs. 0.9% [111隻死亡1隻])。剖檢可見死亡母鼠的胃幽門部出血及腸道充滿凝固性血液;肝臟腫脹且與脾臟皆疲軟蒼白。顯微鏡檢下可發現急性腎小管變性、壞死(karyolysis)及胃黏膜壞死(100%,鏡檢4隻病變皆相同)。總結,使用ketorolac作為ET術後止痛劑,易使CByB6F1小鼠發生腎臟與胃部傷害進而導致急性死亡。

並列摘要


Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) commonly used as a postoperative analgesic in humans and rodents, and is routinely used in pseudopregnant CByB6F1 mice after embryo transfer (ET) surgery. We observed a significantly higher mortality rate in FT mice treated with ketorolac (4 mg/kg SC) than in those treated with ketoprofen (3.3 mg/kg SC) (29% 114 out of 49] vs. 0.9% [1 out of 111], p<0.0001) within 1 to 2 days after FT surgery. Typically, the dead mice had hemorrhage in the gastric pylorus with clotted blood filling the intestine. Swollen liver was noted. Both the liver and kidney were flaccid and pale. Acute renal tubular degeneration and karyolysis as well as gastric mucosa necrosis were noted upon histopathological examination (100%, 4 out of 4 examined). In conclusion, CByB6F1 mice treated with ketorolac after FT were prone to acute renal toxicity and gastric damage resulted in acute death.

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