基于代谢组学评价黄芪提取物对2型糖尿病小鼠代谢紊乱的调节作用  

Evalvation of Astragali Radix Extract on metabolic disorders of type 2 diabetic mice based on metabolomics

作　　者：甘络雯 秦艳 张倩 陈建平 苟小军 李亚娟 GAN Luowen;QIN Yan;ZHANG Qian;CHEN Jianping;GOU Xiaojun;LI Yajuan(Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Pharmacy,The Second Affiliated Hospital of Air Force Medical University,Xi'an 710038,Shaanxi,China;Central Laboratory,Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai,Shanghai 201999,China)

机构地区：[1]上海中医药大学交叉科学研究院,上海201203 [2]空军军医大学第二附属医院药剂科,陕西西安710038 [3]上海市宝山区中西医结合医院中心实验室,上海201999

出　　处：《上海中医药大学学报》2024年第6期82-91,100,共11页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(82074083)。

摘　　要：目的:基于代谢组学方法研究黄芪提取物(AME)改善2型糖尿病(T2DM)小鼠代谢紊乱作用的研究,为黄芪作为临床辅助治疗糖尿病用药提供代谢组学依据。方法:选取雄性C57BL/6小鼠,随机分为正常组、模型组、AME治疗组,采用高脂饲料联合链脲佐菌素(STZ)腹腔注射诱导T2DM小鼠模型,AME组小鼠给予AME(1.5 g/kg)灌胃4周。采用高效液相色谱-线性离子阱串联质谱联用(HPLC-LTQ-Orbitrap Elite-MS/MS)检测血清和肝脏组织代谢情况;检测小鼠血清三酰甘油(TG)、总胆固醇(TC)含量;苏木精-伊红(H-E)染色和油红O染色观察肝脏组织病理形态学变化;采用超高效液相色谱-质谱联用(UPLC-MS/MS)测定AME质量标准。结果:AME可以显著抑制T2DM小鼠体质量下降,降低血清TG、TC水平(P<0.05),显著改善T2DM小鼠肝脏脂质损伤;AME可显著改善T2DM小鼠血清和肝脏中17种代谢物的异常,涉及3条代谢通路:(1)D-谷氨酰胺和D-谷氨酸代谢,(2)丙氨酸、天冬氨酸和谷氨酸代谢,(3)酮体的合成和降解。结论:AME能够显著降低T2DM小鼠血清中TG、TC水平,改善肝脏脂质损伤,并通过多个代谢途径调节T2DM小鼠血清和肝脏代谢紊乱。Objective:To investigate the effect of Astragali Radix extract(AME)on improving metabolic disorders in type 2 diabetes mellitus(T2DM)mice based on metabolomics,and provide metabolomic basis for Astragali membranaceus as a clinical adjuvant drug for the treatment of diabetes.Methods:Male C57BL/6 mice were randomly divided into control group,model group and AME treated group.T2DM mouse model was induced by intraperitoneal injection of high-fat diet combined with streptozocin(STZ).The mice in AME group were treated with AME(1.5 g/kg)by gavage for 4 weeks.The metabolic status of serum and liver tissue was detected by high performance liquid chromatography-linear ion trap quadrupole-orbitrap elite-MS/MS(HPLC-LTQ-Orbitrap Elite-MS/MS).The contents of serum triacylglycerol(TG)and total cholesterol(TC)in mice were tested.The pathomorphology changes of liver tissue were observed by hematoxylineosin(H-E)staining and oil red O staining.The quality standard of AME was determined by UPLC-MS/MS.Results:Weight loss of T2DM mice was significantly inhibited and the levels of serum TG and TC were significantly lowered by AME(P<0.05),and liver lipid damage in T2DM mice was significantly improved.The abnormalities of 17 metabolites in serum and liver of T2DM mice were significantly improved by AME,involving 3 metabolic pathways:(1)D-glutamine and D-glutamate metabolism,(2)alanine,aspartate and glutamate metabolism,(3)synthesis and degradation of ketone bodies.Conclusion:AME could significantly reduce the levels of serum TG and TC,ameliorate liver lipid damage of T2DM mice,and regulate serum and liver metabolic disorders in T2DM mice through multiple metabolic pathways.

关 键 词：黄芪 2型糖尿病 代谢组学 

分 类 号：R285.5[医药卫生—中药学]