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.
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)
出处
《上海中医药大学学报》
CAS
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)。
关键词
黄芪
2型糖尿病
代谢组学
Astragali Radix
type 2 diabetes
metabolomics
作者简介
甘络雯,女,硕士,主要从事中药防治糖尿病研究;共同第一作者:秦艳,女,硕士,主要从事药理学研究;通信作者:李亚娟,副研究员,硕士生导师,E-mail:liyajuan9@sina.cn。;通信作者:苟小军,主任药师,E-mail:gouxiaojun1975@163.com。
