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离体大鼠肾脏灌流技术在发现和评价促尿酸排泄药物中的初步应用
引用本文:朱深银,周远大,刘庆山,杜冠华. 离体大鼠肾脏灌流技术在发现和评价促尿酸排泄药物中的初步应用[J]. 中国药理学通报, 2006, 22(12): 1452-1456
作者姓名:朱深银  周远大  刘庆山  杜冠华
作者单位:1. 中国医学科学院药物研究所,北京,100050;重庆医科大学附一院临床药理研究室,重庆,400016
2. 重庆医科大学附一院临床药理研究室,重庆,400016
3. 中国医学科学院药物研究所,北京,100050;中国药科大学药学院,江苏,南京,210009
4. 中国医学科学院药物研究所,北京,100050
基金项目:国家高技术研究发展计划(863计划)
摘    要:目的为建立发现和评价促尿酸排泄药物作用的离体模型,采用离体大鼠肾脏灌流技术,观察尿酸在离体肾脏中排泄特点和丙磺舒对尿酸排泄影响。方法制备离体大鼠肾脏灌流模型,随机分为对照组和丙磺舒处理组,以含复方氨基酸和65g.L-1牛血清白蛋白的K-H灌流液循环灌流90min,定时收集导尿管流出液和灌流液,测定其中菊粉、钠、葡萄糖及尿酸含量,计算肾功能参数和尿酸排泄情况。结果离体灌流肾脏的肾小球滤过率,尿量,肾小管重吸收水、钠、葡萄糖百分率等肾功能参数在灌流的90min期间处于稳定的生理范围内;对照组灌流肾脏尿酸排泄分数、尿酸清除率及90min内总尿酸排泄量分别为30%、0.30ml.L-1和15μmol,与对照组比较,丙磺舒使离体肾脏尿酸排泄分别提高36%、54%和99%。结论离体大鼠肾脏灌流技术可用于发现和评价促尿酸排泄药物作用。

关 键 词:离体肾脏灌流  尿酸排泄  大鼠
文章编号:1001-1978(2006)12-1452-05
收稿时间:2006-07-30
修稿时间:2006-09-16

Pilot application of isolated perfused rat kidney model for discovery and evaluation of uricosuric drug
ZHU Shen-yin,ZHOU Yuan-da,LIU Qing-shan,DU Guan-hua. Pilot application of isolated perfused rat kidney model for discovery and evaluation of uricosuric drug[J]. Chinese Pharmacological Bulletin, 2006, 22(12): 1452-1456
Authors:ZHU Shen-yin  ZHOU Yuan-da  LIU Qing-shan  DU Guan-hua
Abstract:Aim To establish a in vitro model for discovery and evaluation of uricosuric drug,we established a reliable rat isolated perfused kidney(IPK)preparation and observed urate excretion characterization in absence or presence of probenecid in perfusate by IPK.Methods The IPK model was prepared and perfused in recirculating mode with krebs-henseleit solution containing amino acids,glucose and 65 g·L-1 BSA for 90 min in absence or presence of probenecid,an uricosuric,in perfusate.During the 90 min experimental period,urine was collected in 10 min intervals and perfusate was collected at the midpoint of these intervals.Inulin,glucose,sodium and uric acid levels in urine and perfusate were assayed,kidney functional and uric acid excretion parameters were calculated.Results The kidney functional parameters,glomerular filtration rate(GFR),urine flow rate and percentage tubular reabsorption of water,glucose,and sodium were generally acceptable and stable in both isolated perfused kidney groups throughout the whole experimental period.Fractional excretion of uric acid(FE-UA),clearance of uric acid(Cl-UA)and total urinary UA excretion during 90 min(UA-U)in control group were 30%,0.30 ml·min-1 and 15 μmol,respectively,FE-UA,Cl-UA and UA-U in probenecid group had 36%,54% and 99% increase compared to control group.Conclusion The rat IPK model is a potentially useful tool for drug discovery and evaluation of uricosuric drug.
Keywords:isolated perfused kidney    urate excretion    rat
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