大鼠离体肾灌流技术评价尿肝型脂肪酸结合蛋白在马兜铃酸致肾损伤中的价值

Role of Liver Fatty Acid Binding Protein in Kidney Damage Induced by Aristolochic Acid in Rat Evaluated by Perfusion of Isolated Kidney

摘要:

目的: 探讨大鼠离体肾灌流体系中尿肝型脂肪酸结合蛋白与马兜铃酸(AA)肾损伤的关系。 方法: 建立大鼠离体肾灌流模型,按5 mL ·min^-1恒速灌流,空白组给予正常灌流液,马兜铃酸组给予7 mg ·(50 mL)^-1,灌流给药10 min后,不同时间点收集灌流液和尿液,分别检测钾、钠、氯离子浓度,计算离子清除率,ELISA方法检测尿液肝型脂肪酸结合蛋白浓度。 结果: 马兜铃酸组钾、钠离子清除率在给药后0.5h明显下降,分别从给药前的(99.54±14.55)%和(27.93±6.66)%下降至(33.16±9.59)%和(9.70±2.62)%,与空白组相比差异显著;尿肝型脂肪酸结合蛋白在给药灌流后即刻明显升高,从给药前(7.42±0.12)ng ·L^-1升高至(8.18±0.47)ng ·L^-1,与空白组相比差异显著。 结论: 尿肝型脂肪酸结合蛋白在评价马兜铃酸致急性肾小管损伤方面优于传统指标离子清除率,是一个早期且敏感的肾小管损伤生物标志物。

Abstract:

Objective: To discuss the relationship between the liver fatty acid binding protein and kidney damage induced by aristolochic acid in rats evaluated by perfusion of isolated kidney. Method: Rat perfusion model of isolated kidney was established at the constant flow of 5 mL ·min^-1.The control group was administrated with normal perfusate,while the experimental group was given aristolochic acid(7 mg in 50 mL).After 10 min of perfusion, the perfusate and urine at different time points were collected.Then concentration of K,Na,Cl was determined and their clearance was calculated.The content of liver fatty acid binding protein was detected by Elisa. Result: Compared with the control group,the clearance of K and Na in the experimental group given aristolochic acid began to decrease from (99.54±14.55)% and (27.93±6.66)% of pre-perfusion to (33.16±9.59)% and (9.70±2.62)% of 30 min after perfusion respectively,and liver fatty acid binding protein immediately increased significantly from (7.42±0.12)ng ·L^-1 of pre-perfusion to (8.18±0.47)ng ·L^-1 at the moment of after perfusion respectively. Conclusion: Liver fatty acid binding protein is superior to the clearance of traditional indicators in the evaluation of acute tubular injury induced by aristolochic acid.It is an early and sensitive biomarker of renal tubular injury.