邹丽娜 王雨 姜卓希 巨珊珊 张冰 林志健 杨婷

摘要 目的：基于腎脏尿酸转运环节，筛选及评价中药降尿酸活性成分，为阐释中药降尿酸物质基础提供理论和技术支撑。方法：以不同灌注压力进行大鼠离体肾脏灌流，通过肾小球滤过率、尿流率、葡萄糖重吸收率、钠离子重吸收率、钾离子重吸收率等评价肾功能，建立离体肾脏模型;设置尿酸组、菊苣酸组和丙磺舒组进行离体肾脏灌流，观察肾脏尿酸排泄情况，以菊苣酸示例应用离体肾脏灌流模型;设置对照组、尿酸组、苯溴马隆组、丙磺舒组及菊苣酸组，通过蛋白免疫印迹法检测高尿酸状态下HKC细胞GLUT9蛋白表达变化，及高尿酸状态下菊苣酸干预后的表达变化，结合离体肾脏灌流技术评价降尿酸活性成分。结果：在120 mm Hg（1 mm Hg=0.133 kPa）灌注压力下离体肾功能良好;菊苣酸在20～40 min、40～60 min均能提高肾脏清除率，增加肾脏尿酸排泄分数;且菊苣酸能够显著抑制高尿酸状态下HKC细胞的GLUT9蛋白表达。结论：该研究基于肾脏尿酸转运环节，应用离体肾脏灌流技术结合体外HKC细胞筛选并评价中药降尿酸活性成分，筛选出菊苣酸可能是菊苣通过促进尿酸排泄发挥降尿酸作用的活性成分，为抗高尿酸血症药物的研发奠定实验基础，为中药的开发和临床应用提供实验依据，以更好服务于临床。

关键词 降尿酸;活性成分;离体肾脏灌流;HKC;筛选及评价

Screening and Evaluation of Active Ingredients of Traditional Chinese Medicine For Lowering Uric Acid Based on Renal Uric Acid Transport：a Case Study of Cichoric Acid

ZOU Lina，WANG Yu，JIANG Zhuoxi，JU Shanshan，ZHANG Bing，LIN Zhijian，YANG Ting

（School of Chinese Materia Medica，Beijing University of Chinese Medicine，Beijing 102488，China）

Abstract Objective：Based on the kidney uric acid transport link，to screen and evaluate the active ingredients of traditional Chinese medicine for lowering uric acid，providing theoretical and technical support for the interpretation of the material basis of traditional Chinese medicine（TCM）for lowering uric acid.Methods：The isolated rat kidneys was perfused with different perfusion pressures.The renal function was evaluated by glomerular filtration rate，urine flow rate，glucose reabsorption rate，sodium ion reabsorption rate，potassium ion reabsorption rate，etc.，and the isolated kidney model was established.The uric acid group，the cichoric acid group and the probenecid group for isolated kidney perfusion were set，the renal uric acid excretion was observed.Western blotting was used to detect the changes in the expression of GLUT9 protein in HKC cells under high uric acid conditions and the changes in the expression of cichoric acid intervention under high uric acid conditions，and to evaluate the uric acid-lowering active ingredients combined with isolated kidney perfusion technology.Results：The isolated kidney function was good under 120 mm Hg perfusion pressure; cichoric acid can improve renal clearance and increase renal uric acid excretion at 20-40 min and 40-60 min; cichoric acid can increase renal uric acid excretion fraction; and cichoric acid can significantly inhibit the expression of GLUT9 protein in the state of high uric acid.Conclusion：The study is based on the transport of uric acid in the kidney.By applying isolated kidney perfusion technology combined with in vitro HKC cells，the active ingredients of TCM for lowering uric acid are screened and evaluated.Cichoric acid screened out may be the active ingredient of chicory to lower uric acid by promoting uric acid excretion，laying an experimental foundation for the research and development of anti-hyperuricemia drugs，and providing experimental evidence for the development and clinical application of traditional Chinese medicine to better serve clinical practices.

Keywords Lowering uric acid; Active ingredient; Isolated kidney perfusion; HKC; Screening and evaluation

中图分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.01.005

临床研究结果显示，90%左右的原发性高尿酸血症属于尿酸排泄不良型[1]。……