基于代谢组学分析金芪降糖片改善2型糖尿病大鼠脂代谢紊乱的作用机制  

Mechanism of Jinqi Jiangtang Tablets on Improving Lipid Metabolism Disorder of Type 2 Diabetic Rats Based on Metabonomics

作　　者：陈瑞 马宁宁 范姗姗 尹清晟 韩娟[1] 贺云杰[2] 朱晓丹[2] 刘新元 张艳军[1] 庄朋伟[1] 宋丽丽[1] CHEN Rui;MA Ning-ning;FAN Shan-shan;YIN Qing-sheng;HAN Juan;HE Yun-jie;ZHU Xiao-dan;LIU Xin-yuan;ZHANG Yan-jun;ZHUANG Peng-wei;SONG Li-li(Tianjin Key Laboratory of Pharmacology of Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;Longshunrong Pharmaceutical Factory,Tianjin Zhongxin Pharmaceutical Group Co.Ltd.,Tianjin 300457,China)

机构地区：[1]天津中医药大学天津市中药药理学重点实验室,天津300193 [2]天津中新药业集团股份有限公司隆顺榕制药厂,天津300457

出　　处：《中国实验方剂学杂志》2018年第20期102-107,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家教育部长江学者和创新团队发展计划项目(IRT_14R41)

摘　　要：目的：从代谢组学角度探究金芪降糖片改善2型糖尿病大鼠脂代谢紊乱的作用机制。方法：雄性Wistar大鼠45只,采用高脂饲料喂养联合3次小剂量腹腔注射链脲霉素（STZ,35 mg·kg^（-1））复制2型糖尿病模型,造模成功后随机分为正常组、模型组、金芪降糖片组。金芪降糖片组连续给药4周,给药结束后腹主动脉取血,利用半自动生化分析仪检测血脂水平,苏木精-伊红（HE）染色观察肝脏病理变化;采用UPLC-Q-TOF-MS对不同组别的血液样本进行检测,运用主成分分析（PCA）和偏最小二乘法-判别分析（PLS-DA）筛选正常组、模型组和金芪降糖片组之间的差异代谢物,结合质谱信息和公共数据库检索对差异代谢物进行鉴定并进行京都基因与基因组百科全书（KEGG）代谢通路分析。结果：与正常组比较,模型组大鼠血脂水平明显升高,金芪降糖片组血脂较模型组明显下降,模型组肝脏出现明显的脂肪粒细胞,金芪降糖片组肝细胞脂肪粒明显减少。模型组和正常组大鼠有12种内源性物质发生了显著性变化,经金芪降糖片干预后花生四烯酸,左旋肉碱,溶血磷脂酰胆碱（LysoPC）（17∶0）,LysoPC（P-18∶0）,LysoPC[22∶4（7Z,10Z,13Z,16Z）],硬脂酰肉碱这6种代谢物水平出现了不同程度的回调,得到1条关键代谢通路——花生四烯酸代谢通路。结论：金芪降糖片对2型糖尿病脂代谢紊乱大鼠体内的差异代谢物有一定的回调作用,其作用机制主要与花生四烯酸代谢通路有关。Objective： To explore the mechanism of Jinqi Jiangtang tablets on improving lipid metabolism disorder in type 2 diabetic rats from the perspective of metabonomics. Method： Type 2 diabetes mellitus model was established in 45 male Wistar rats fed with high fat diet and 3 times of intraperitoneal injection of streptozotocin（ STZ,35 mg·kg^（-1））. After successful modeling,the rats were randomly divided into normal group,model group and Jinqi Jiangtang tablets group. Jinqi Jiangtang tablets group was administered continuously for 4 weeks. At the end of administration,the blood was taken from the abdominal aorta and the blood lipid level was detected by a semi automatic biochemical analyzer,the pathological changes of the liver were observed by hematoxylin-eosin（ HE） staining; the blood samples in different groups were detected by UPLC-Q-TOF-MS. Principal component analysis（ PCA） and partial least squares-discriminant analysis（ PLS-DA） were used to screen the differential metabolites among the normal group,model group and Jinqi Jiangtang tablets group,these differential metabolites were identified by mass spectrometry information and public database retrieval,and their metabolic pathways of the Kyoto encyclopedia of genes and genomes（ KEGG） were analyzed. Result： Compared with the normal group,the level of blood lipid in the model group was significantly increased,the serum lipids in Jinqi Jiangtang tablets group were significantly lower than those in the model group. In the model group,obvious fatty granulocytes appeared in the liver,the hepatocyte fat granulocytes were significantly decreased in the administration group. There were 12 kinds of endogenous substances with significant changes in type 2 diabetes mellitus model group and the normal group. After intervention with Jinqi Jiangtang tablets, the levels of arachidonic acid, L-carnitine, lysophosphatidylcholine（ LysoPC）（ 17 ∶ 0）,LysoPC（ P-18 ∶ 0）,LysoPC [22 ∶ 4（ 7 Z,10 Z,13 Z,16 Z） ] and stearyl carnitine show

关 键 词：金芪降糖片 代谢组学 2型糖尿病 脂代谢紊乱 生物标志物 花生四烯酸 溶血磷脂酰胆碱 

分 类 号：R22[医药卫生—中医基础理论] R969.1[医药卫生—中医学]