犬药物性急性肾损伤模型的建立及评价

目的]探讨建立犬药物性急性肾损伤模型。方法]16只健康成年比格犬每8 h皮下注射20 mg/kg庆大霉素,注射前血肌酐浓度(SCr)作为基线,注射后每6 h采集血液检测SCr浓度,于SCr无明显升高、SCr升高临近正常值上限及SCr升高到基线1.5倍时观察肾组织病理形态学改变,确定犬药物性急性肾损伤模型。结果]SCr在注射庆大霉素后78 h显著升高(P<0.05),实验犬SCr均在120～132 h达到基线的1.5倍;肾组织在SCr升高到基线1.5倍时肾皮质大面积的肾小管变性、坏死,管腔有较多的细胞碎片和颗粒管型,基底膜裸露明显,髓质损伤较轻;与健康对照组相比,注射后肾损伤评分差异有统计学意义(P<0.05),且肾损伤随用药时间延长评分逐渐增加。结论]庆大霉素每8 h皮下注射20 mg/kg直至SCr浓度升高到基线1.5倍的方法可成功建立犬药物性急性肾损伤模型。

Establishment and Evaluation of a Drug-induced Acute Renal Injury Model in Dog

Objective] To establish a drug-induced acute kidney injury model in dog.Method] A total of 16 healthy adult beagle dogs were subcutaneously injected with 20 mg/kg gentamicin every 8 h.The serum creatinine concentration (SCr) before injection was used as the baseline,and the blood samples were recovered every 6 h after injection to determine the SCr.When there was no significant increase in SCr,SCr increased near the upper limit of normal value,and SCr increased 1.5 times to baseline,the pathological changes of renal tissue were observed,and the model of canine drug-induced acute kidney injury was determined.Result] SCr was significantly increased at 78 h post gentamicin injection (P<0.05).The SCr of the tested dogs reached 1.5 times of the baseline during 120 h to 132 h post injection.When the SCr was 1.5 times higher than that of the baseline,the following pathological changes were observed: extensive degeneration and necrosis of renal tubules in renal cortex,increased cell debris and granules in lumen of renal tubules,the bare basement membrane,and the minor damage in renal medulla.Compared with the healthy controls,the difference in renal injury score after injection was statistically significant (P<0.05),and the renal injury gradually deteriorated with the prolonged medication time.Conclusion] A model of canine drug-induced acute kidney injury can be successfully established by subcutaneous injection of 20 mg/kg of gentamicin every 8 h till the SCr was 1.5 times higher than that of the baseline.