急、慢性高尿酸血症模型的建立  

Establishment of mouse and rat models of acute and chronic experimental hyperuricemia

作　　者：冯学轩 刘月姝[1] 饶子亮[1] 黎耀俊[1] 潘晓慧 姚嘉琪[1] 郭起岳[1] 王诺[1] 邝少松[1] FENG Xuexuan;LIU Yueshu;RAO Ziliang;LI Yaojun;PAN Xiaohui;YAO Jiaqi;GUO Qiyue;WANG Nuo;KUANG Shaosong(Guangdong Medical Laboratory Animal Center,Guangzhou 528248,China)

机构地区：[1]广东省医学实验动物中心

出　　处：《中国比较医学杂志》2020年第1期74-80,共7页Chinese Journal of Comparative Medicine

摘　　要：目的拟通过建立急性小鼠与慢性大鼠高尿酸血症模型,并采用阳性药验证两种模型的可治愈性,为抗高尿酸药物的研发提供模型工具。方法急性痛风模型小鼠采用腹腔注射次黄嘌呤联合皮下注射氧嗪酸钾的方法造模,造模后半小时阳性组给予别嘌醇片,造模后2 h测定血尿酸、血肌酐、血清尿素氮及肝黄嘌呤氧化酶(XOD)活性。慢性痛风大鼠每天灌胃腺嘌呤及乙胺丁醇盐酸盐造模,阳性组每天给予别嘌醇片,连续21 d后检测血尿酸、血肌酐、血清尿素氮、肝XOD活性并进行肾组织病理学检测。结果急、慢性痛风模型动物血尿酸、血肌酐均显著升高(P<0.05),慢性痛风大鼠还可见血清尿素氮及肝XOD活性显著升高(P<0.05),肾小管间质损伤及尿酸盐结晶加重,评分显著升高(P<0.05)。阳性药别嘌醇可显著降低急、慢性高尿酸动物的血尿酸值,降低慢性高尿酸动物的血肌酐值、肝XOD活性,改善肾损伤及减少尿酸盐结晶(P<0.05)。结论本实验所采用的方法适用于建立急、慢性高尿酸血症动物模型,并可用于药物药效学观察。Objective To provide approaches for modeling the development of anti-hyperuricemia drugs,acute and chronic hyperuricemia animal models were established,and positive drug was applied to verify the curability of these two animal models.Methods The acute hyperuricemia mouse model was established by the intraperitoneal injection of hypoxanthine and subcutaneous injection of oteracil potassium.Allopurinol tablets were administered to the positive group half an hour after the model establishment.Finally,the concentrations of serum uric acid,serum creatinine,and serum urea nitrogen and the activity of liver xanthine oxidase(XOD)were determined 2 h after model establishment.In contrast,adenine and ethambutol dihydrochloride were used to establish the chronic hyperuricemia rat model by gavage.The positive group was administered allopurinol tablets daily.After 21 days,the concentrations of serum uric acid,serum creatinine,and serum urea nitrogen,the activity of XOD,and the histopathological change of kidneys were determined.Results The concentrations of serum uric acid and serum creatinine were significantly elevated(P<0.05)in both the acute and the chronic hyperuricemia models.Additionally,serum urea nitrogen and XOD activity were also clearly elevated(P<0.05),while renal tubule interstitial injury and urate crystallization could be found,the scores of which were significantly increased in the chronic hyperuricemia model.However,the concentration of serum uric acid was decreased after treatment with allopurinol tablets for both acute and chronic hyperuricemia animals;moreover,in the chronic hyperuricemia animals,the concentration of serum creatinine and activity of liver XOD were decreased,while kidney injury and urate crystallization were also improved.Conclusions The approaches established in this study are suitable for creating acute and chronic hyperuricemia animal models,and can be used for drug pharmacodynamic observation.

关 键 词：急性高尿酸血症 慢性高尿酸血症 血生化 肾损伤 尿酸盐结晶 组织病理学 小鼠 大鼠 

分 类 号：R-33[医药卫生]