大鼠离体肾脏灌流模型在筛选慢性肾病药物的初步应用

doi:10.3969/j.issn.1674-5817.2017.05.004

摘要/Abstract

摘要： 目的在慢性肾病(CKD)转基因大鼠建立大鼠离体肾脏灌流(IPK)模型,为CKD药物药效学研究提供可靠的工具。方法在患有CKD的转基因大鼠(n=7)建立稳定的IPK模型后,灌流1 μmol/L环孢素A(CysA) 60 min,与未灌流CysA前相比,检测尿液中白蛋白含量的变化。同时,通过CKD转基因大鼠(n=5)体内实验,连续灌胃给药20 mg/kg CysA 15日, 验证CysA改变尿液中白蛋白水平的作用。结果用1 μmol/L的CysA 灌流7只患有CKD的转基因大鼠60 min后显示,CysA具有显著的降低白蛋白尿水平的作用。体内药效学实验,连续灌胃给药20 mg/kg CysA 15日后,CysA也具有显著的降低白蛋白尿水平的作用。结论 CysA在IPK模型和体内药效学实验结果一致,成功地建立CKD转基因大鼠IPK模型,该模型可作为CKD药物药效学研究的工具。

关键词: 离体肾脏灌流(IPK), 环孢素A(CysA), 慢性肾病(CKD)

Abstract: Objective To establish isolated perfused kidney (IPK) model in chronic kidney disease (CKD) transgenic rat, as a screening tool for CKD drug. Method Seven CKD transgenic rats were perfused with 1 μmol/L CysA for 60 minutes, the content of albumin in urine were detected before and after treatment to evaluate the effect of CysA. Five CKD transgenic rats were treated with 20 mg/kg CysA/day for 15 days, the content of albumin in urine were compared to 5 control CKD transgenic rats to evaluate in vivo effect of CysA. Results After perfusing 1 μmol/L CysA for 60 minutes, the content of albumin in urine were decrease signicantly. In in vivo efficacy study,after dosing CysA 15days, the content of albumin in urine were also decrease signicantly. Conclusion The consistency of CysA efficacy of decreasing the content of albumin in urine bewteen IPK model and in vivo animal model in CKD transgenic rat is good. The IPK model on CKD transgenic rat have potential to be a further screening tool for CKD drug.

Key words: Isolated perfused kidney(IPK), Cyclosporin A (CysA), Chronic kidney disease (CKD)

中图分类号:

Q95-33

傅婷婷, 刘艳. 大鼠离体肾脏灌流模型在筛选慢性肾病药物的初步应用[J]. 实验动物与比较医学, 2017, 37(5): 357-362.

FU Ting-ting, LIU Yan. Pilot Application of Isolated Perfused Chronic Kidney Transgenic Rat Kidney Model for Discovery and Evaluation of Chronic Kidney Disease Drug[J]. Laboratory Animal and Comparative Medicine, 2017, 37(5): 357-362.

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