基于代谢组学对化浊解毒方治疗2型糖尿病大鼠的糖脂代谢研究  

A metabolomics-based strategy for Huazhuo Jiedu Formula in the treatment of rat with type 2 diabetes mellitus

作　　者：何百川[1] 章清华[2] 薛超[1] 吴深涛[2] 

机构地区：[1]天津中医药大学研究生院,天津300193 [2]天津中医药大学第一附属医院,天津300193

出　　处：《中华中医药杂志》2016年第5期1897-1900,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金资助项目(No.81273710)~~

摘　　要：目的:应用代谢组学方法探讨化浊解毒方改善2型糖尿病大鼠的糖脂代谢机制。方法:高脂饮食加尾静脉小剂量注射链脲佐菌素(28mg/kg)建立2型糖尿病大鼠模型,将造模成功的大鼠随机分为5组:模型组,化浊解毒低(生药1.5g·kg-1·d-1)、中(生药3.0g·kg-1·d-1)、高(生药6.0g·kg-1·d-1)剂量组,吡格列酮组(3.0mg·kg-1·d-1),另取同周龄健康大鼠10只作为空白对照组。给药组每日灌胃给药1次,连续给药4周;模型组和空白对照组给予同体积的0.9%氯化钠溶液灌胃。给药4周后,采用葡萄糖氧化酶法测定大鼠空腹血糖(FBG),放射免疫法测定空腹胰岛素(FINS),全自动生化分析仪检测大鼠的甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA);采用超高效液相色谱-飞行时间质谱连用技术(UPLC-TOFMS)对大鼠肝脏样本中的内源性物质进行了相对含量测定。结果:化浊解毒方对高脂饮食联合小剂量链脲佐菌素诱导的糖尿病大鼠血糖、血脂紊乱有明显的治疗作用。并通过代谢组学及主成分分析可得出,空白对照组与模型组显著分离,化浊解毒低、中、高剂量组处于空白对照组与模型组之间,且更接近于空白对照组,同时具有剂量依赖差异。通过数据处理发现其改善2型糖尿病大鼠的糖脂代谢与胆汁酸、磷脂等9个代谢物有关。结论:化浊解毒方可明显改善2型糖尿病大鼠的糖脂代谢,其潜在机制与肝脏内胆汁酸、磷脂、视晶酸等代谢具有一定相关性。Objective： To investigate the mechanism of Huazhuo Jiedu Formula（HZJF） in the treatment of rat with type 2 diabetes mellitus（T2DM） through metabolomics study. Methods： The T2 DM rat model was established by high-fat diet combined with an injection of low dose of streptozocin（28mg/kg）. The T2 DM rats were randomly divided into five groups, including model group, low dose of HZJF group（1.5g · kg-1 · d-1, i.g）, middle dose of HZJF group（3.0g · kg-1 · d-1, i.g）, high dose of HZJF group（6.0g · kg-1 · d-1, i.g） and pioglitazone group（3.0mg · kg-1 · d-1, i.g）. In addition, another 10 healthy rats with the same week old were treated as the control group. All drug administration groups were respectively given the drugs by gavage, once a day, continuously for 4 weeks, while the control group and model group were given normal saline. The glucose oxidase method was used to detect the level of fasting blood glucose（FBG）, and the radioimmunoassay method was used to detect the level of fasting serum insulin（FINS）. The fully automatic biochemical analyzer was used to detect the levels of triglyceride（TG）, total cholesterol（TC） and free fatty acid（FFA）. Besides, the relative content of endogenous substances in rat liver samples was detected by UPLC-TOFMS. Results： Our data demonstrated that HZJF dramatically improved the disorder of blood glucose and blood lipid in the rat induced by high-fat diet combined with an injection of low dose of STZ. From metabolomics study, principal component analysis（PCA） indicated that the control group was significantly disturbed far from the model group, and different dose of HZJF treated groups scattered more closely to the control group and at the same time it had a dose-dependent. Thus, the pharmacological effect of HZJF on T2 DM rats was further confirmed by the investigation of metabolomics. From our results, bile acids, phosphatidylcholine and ophthalmic acid were discovered by PCA analysis, all of which contributed most to th

关 键 词：2型糖尿病 化浊解毒 代谢组学 糖代谢 脂代谢 

分 类 号：R259[医药卫生—中西医结合]