蛹虫草提取物改善糖尿病肾病的药效及代谢组学  

Pharmacodynamic and metabolomic studies of cordyceps militaris extract in improving diabetic nephropathy

作　　者：金鑫 孙雪琳 刘虹拴 马庆云 李志浩 李申莹 黄盛 张琪[1] JIN Xin;SUN Xuelin;LIU Hongshuan;MA Qingyun;LI Zhihao;LI Shenying;HUANG Sheng;ZHANG Qi(School of Pharmaceutical Sciences,Nanjing Tech University,Nanjing 211800,China;School of Pharmany,China Pharmacentical University,Nanjing 211198,China)

机构地区：[1]南京工业大学药学院,江苏南京211800 [2]中国药科大学药学院,江苏南京211198

出　　处：《生物加工过程》2025年第1期77-85,共9页Chinese Journal of Bioprocess Engineering

基　　金：江苏省科技计划社会发展重点项目(BE2019737);南京工业大学“大学生创新创业与实践开放基金”(2021DC1021)。

摘　　要：基于气相色谱联用质谱(GC-MS)的代谢组学和药效学,评估蛹虫草提取物中虫草素与虫草寡糖联合用药对小鼠糖尿病肾病的改善作用及其作用机制。采用链脲佐菌素(STZ)联合高脂饮食建立2型糖尿病小鼠模型,将小鼠随机分为空白组、模型组、虫草素组、虫草寡糖组和联用组。给药8周,其间每两周测定各组小鼠血糖浓度。8周后,测定肾脏指数;苏木精-伊红(HE)染色评估小鼠肾组织形态。同时通过气相色谱联用质谱(GC-MS)进行血清代谢组学研究。结果表明:成功建立了小鼠糖尿病肾病的模型;虫草寡糖组和联用组均有降血糖作用;虫草素组、虫草寡糖组和联用组均能显著降低肾脏指数,同时显著改善肾组织形态。代谢组学结果表明:空白组和模型组能够很好地分离,虫草素组、虫草寡糖组和联用组更趋近于空白组。与空白组比较,模型组血清内L-酪氨酸、L-丙氨酸和焦磷酸盐等代谢物差异显著[变量投影重要性(VIP)>1,P<0.05]。本研究表明:蛹虫草提取物中虫草素与虫草寡糖的联合用药对糖尿病肾病具有降血糖作用,能显著降低肾脏指数,还可以改善肾组织形态,这为蛹虫草提取物的临床应用提供了一定的理论基础,并为改善糖尿病肾病的治疗提供了新的思路。The effects of the combination of cordycepin and cordycepins oligosaccharide in codyceps militaris extract on the improvement of diabetic nephropathy of mice was evaluated using pharmacodynamics and metabonomics of gas chromatography-mass spectrometry(GC-MS).A mouse model of diabetes was established by administration of streptozotocin(STZ)with a high-fat diet.Mice were randomly divided into the following five groups:control group,model group,cordycepin group,cordycepins oligosaccharide group,and cordycepin combined with cordycepins oligosaccharide group.During 8 weeks of administration,blood glucose was measured in each group every two weeks.At the end of 8 weeks studies,the renal index was determined.HE staining was used to evaluate the morphology of mouse kidney tissue,and serum metabolomics was investigated by GC-MS.Based on the results,the model of diabetic nephropathy in mice was established successfully.Both the cordycepins oligosaccharide group and the cordycepin combined with cordycepins oligosaccharide group had hypoglycemic effect.Cordycepin group,cordycepins oligosaccharide group and cordycepin combined with cordycepins oligosaccherid group could significantly improve rend tissue morphology.Based on metabolomics results,the control group and the model group showed excellent separation,and the other three groups(cordycepin group,cordyceps oligosaccharides group and cordycepin combined with cordycepins oligosaccharide group)were closer to the control group.Compared with control group,model group showed significant difference for kinds of metabolites such as L-tyrosine,L-alanine and pyrophosphate in serum[variable importance in the projection(VIP)>1,P<0.05].Overall,the combination of cordycepin and cordycepins oligosaccharide in cordyceps militaris extract showed hypoglycemic effects on diabetic nephropathy,leading to significant reduction of renal index and improvement of renal tissue morphology.This provides a theoretical basis for the clinical application of cordyceps militaris extract and a new idea f

关 键 词：糖尿病肾病 蛹虫草提取物 代谢组学 虫草素 

分 类 号：R965[医药卫生—药理学]