急性慢性高尿酸血症大鼠模型的建立  

Establishment of Acute and Chronic Hyperuricemia Models of Rats

作　　者：张馨 崔娜 侯俊玲[1,3] 王文全[3,4] ZHANG Xin;CUI Na;HOU Junling;WANG Wenquan(School of Chinese Pharmacy,Beijing University of Chinese Medicine,Beijing 100102,China;Lang Fang Aidebao Hospital,Langfang 065000,China;Engineering Research Center of GAP for Chinese Crude Drugs,Ministry of Education,Beijing 100102,China;Chinese Academy of Medical Sciences/Peking Union Medical College Institute of Medicinal Plant Development,Beijing 100193,China)

机构地区：[1]北京中医药大学中药学院,北京100102 [2]廊坊爱德堡医院,廊坊065000 [3]中药材规范化生产教育部工程研究中心,北京100102 [4]中国医学科学院/北京协和医学院/药用植物研究所,北京100193

出　　处：《世界中医药》2023年第16期2309-2313,2318,共6页World Chinese Medicine

基　　金：国家重点研发计划项目(2018YFC1706500)——甘草全产业链技术体系升级与产品开发。

摘　　要：目的:筛选出稳定可行的急性、慢性高尿酸血症大鼠模型,为抗高尿酸药物的研发提供模型工具。方法:急性高尿酸血症大鼠模型采用皮下注射次黄嘌呤(HX)+腹腔注射氧嗪酸钾(OAPS)和单纯腹腔注射OAPS的方法造模,在造模后0 h、1 h、2 h、4 h、8 h、10 h眼眶取血,测定血尿酸、血肌酐及血清尿素氮水平。慢性高尿酸血症大鼠每天灌胃酵母膏(YE)+腺嘌呤(AP)溶液+定期腹腔注射OAPS溶液和每天灌胃乙胺丁醇(EMB)+OAPS混合溶液的方式造模,连续给药14 d,停止给药后继续观察14 d,在第4、6、8、11、14、15、16、18、20、22、25、28天大鼠眼眶取血检测血尿酸、血肌酐、血清尿素氮,在第14、28天取大鼠肾脏进行肾组织病理学检测。结果:2种急性模型均出现了尿酸值短暂性升高和急性肾脏损伤情况,而HX+OAPS联合模型高尿酸水平维持时间更长。2种慢性模型尿酸水平显著提高并出现了肾脏损伤,停止造模后,2种高尿酸水平可以维持1周左右,EMB+OAPS给药肾脏损伤更加严重,2周后各项指标仍处于高水平。结论:4种方法均可建立急性慢性高尿酸血症动物模型,但是HX+OAPS联合给药的急性模型和灌胃EMB+OAPS混合溶液的慢性模型病理症状更加明显,维持时间也更长,更适于药物的筛选。Objective:This study aims to screen stable acute and chronic hyperuricemia models of rats to provide a model tool for the research and development of anti-hyperuricemia drugs.Methods:The rat model of acute hyperuricemia was established by subcutaneous injection of hypoxanthine(HX)+intraperitoneal injection of potassium oxonate(OAPS)and only intraperitoneal injection of potassium oxonate(OAPS).Blood samples were taken from the orbit of rats 0,1,2,4,8,and 10 hours after modeling,and the levels of serum uric acid,serum creatinine,and serum urea nitrogen were measured.The rat model of chronic hyperuricemia was established by intragastric administration of yeast extract(YE)+adenine phosphate(AP)+regular intraperitoneal injection of potassium oxonate solution(OAPS)and intragastric administration of ethambutol(EMB)+potassium oxonate(OAPS)solution for 14 days,and the observation continued for 14 days after stopping administration.Blood samples were taken from the orbit of rats on the 4th,6th,8th,11th,14th,15th,16th,18th,20th,22nd,25th,and 28th day,and the levels of serum uric acid,serum creatinine,and serum urea nitrogen were measured.The kidneys were taken for renal histopathological examination on the 14th and 28th day.Results:Both acute models showed significantly increased uric acid and renal injury.After the model-making stopped,the uric acid levels could be maintained for about one week.The renal injury of EMB+OAPS was more serious,and the indexes were still at a high level two weeks later.Conclusion:The above four methods can establish animal models of acute and chronic hyperuricemia.The acute models of HX+OAPS and the chronic model of EMB+OAPS have more obvious pathological symptoms and longer duration,which are more suitable for drug screening.

关 键 词：高尿酸血症 动物模型 大鼠 肾损伤 氧嗪酸钾 血尿酸 血肌酐 血清尿素氮 

分 类 号：R229[医药卫生—中医基础理论]