糖尿病肾病血瘀证动物模型的建立及代谢组学分析  

Establishment of animal model of blood stasis syndrome in diabetic kidneydisease and metabonomic analysis

作　　者：郭倩 万生芳 李荣科 张磊 魏昭晖 仲子惠 邵晶 GUO Qian;WAN Sheng-fang;LI Rong-ke;ZHANG Lei;WEI Zhao-hui;ZHONG Zi-hui;SHAO Jing(School of Basic Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China;Dunhuang Key Lab of Medicine and Transformation,Ministry of Education,Gansu University of Chinese Medicine,Lanzhou 730000,China;College of Pharmacy,Gansu University of Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学基础医学院,甘肃兰州730000 [2]甘肃中医药大学敦煌医学与转化教育部重点实验室,甘肃兰州730000 [3]甘肃中医药大学药学院,甘肃兰州730000

出　　处：《中国药理学通报》2025年第3期592-599,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82060914);甘肃中医药大学2022年度中医学一级学科“岐黄英才”导师专项基金(博导-6、硕导-12);敦煌医学与转化教育部重点实验室开放课题(No DHYX23-02)。

摘　　要：目的建立糖尿病肾病(diabetic kidney disease,DKD)血瘀证病证结合动物模型及评价指标。方法将25只SD大鼠按体质量随机分为正常组(8只)、造模组(17只)。造模组采用高糖高脂饲料喂养4周,腹腔注射链脲佐菌素30 mg·kg^(-1)诱导建立糖尿病大鼠模型。将成模大鼠按24 h尿蛋白(24-hour urinary protein,24-hUP)随机分为DKD组、血瘀病证结合组,血瘀病证结合组按0.05 mg·kg^(-1)尾静脉注射10%大分子右旋糖苷3次,诱导成DKD血瘀证模型。根据随机血糖、24-hUP、证候评估、病理染色等对模型进行评价,并结合代谢组学方法筛选出差异代谢物。结果血瘀病证结合组大鼠证候评估及病理染色均显示模型复制成功。液质联用技术鉴定出22个差异代谢产物,其涉及的通路也与DKD血瘀证存在一定相关性。结论本次DKD血瘀证病证结合动物模型复制成功,指标评估及代谢组学结果均显示出与DKD血瘀证相关联。Aim To establish an animal model of diabetic kidney disease(DKD)integrating blood stasis syndrome and syndrome evaluation indicators.Methods Twenty-five SD rats were randomly divided according to body weight into a control group(8 rats)and a modeling group(17 rats).The modeling group was fed a high-sugar and high-fat diet for four weeks and induced to form diabetic rats by intraperitoneal injection of 30 mg·kg^(-1) streptozocin.The modeling rats were randomly divided into the DKD group and blood stasis syndrome combination group according to 24-hour urinary protein(24-hUP).The blood stasis syndrome combination group was induced to replicate the DKD blood stasis syndrome model by injecting 10%high molecular weight D-glucoside three times at a dose of 0.05 mg·kg^(-1) via tail vein.The model was evaluated based on random blood glucose level,24-hUP level,syndrome assessment,pathological staining etc,and differential metabolites were selected using metabolomics.Results The comprehensive evaluation of syndrome manifestations and pathological staining in the combined model of blood stasis syndrome in rats demonstrated successful replication.Utilizing the technique of liquid chromatography-mass spectrometry,22 differential metabolites were identified,with associated pathways showing a certain relevance to blood stasis syndrome in DKD.Conclusions The successful replication of an animal model combining the syndrome of blood stasis in DKD has been achieved in this study.Evaluation of indicators and results from metabolomics studies consistently demonstrate a correlation with the syndrome of blood stasis in DKD.

关 键 词：糖尿病肾病 血瘀证 代谢组学 液质联用技术 差异代谢物 代谢通路 

分 类 号：R-332[医药卫生] R255.7R322.61R587.2R692.39