[目的]基于气相色谱-质谱联用技术（GC-MS）分析Ⅱ型糖尿病模型大鼠尿液代谢谱的变化，研究Ⅱ型糖尿病的代谢组学特征及与其密切相关的小分子生物代谢产物，为Ⅱ型糖尿病病机研究提供一种新思路。[方法]SD大鼠高脂饲料喂养9周，于第4周末腹腔注射链脲佐菌素30 mg· kg-1建立Ⅱ型糖尿病大鼠模型。成模后继续高脂饲料喂养4周，动态监测大鼠空腹血糖（FBG）变化，检测甘油三酯（TG）、总胆固醇（CHO）和空腹血清胰岛素（FINS）水平。分别收集大鼠0-9周尿液，采用三甲基硅烷（TMCS）衍生和气相色谱-质谱联用检测大鼠尿液代谢谱的变化。[结果]造模后大鼠FBG持续升高，TG和CHO明显升高，血清FINS含量明显降低；随着时间变化，正常对照组和模型对照组大鼠之间代谢轮廓差异变大；比较两组差异，从差异变量中鉴定出14个生物学标记物。[结论]基于GC-MS的代谢组学方法能反映正常组与模型组动物的尿液样本之间，正常对照组和模型组组内代谢轮廓随着时间推移的分离和靠近的趋势，代谢组学在一定程度上反映Ⅱ型糖尿病大鼠的病理变化。% [Objective]Analyzing metabolic profiling changes in urine of type 2 diabetic rat model based on gas chromatography-mass spectrometry tech-nology(GC-MS), to explore the metabonomics character and micromolecule marking compound closely related to type 2 diabetes. And proviede a new idea for the research of pathogenesis of type 2 diabetes. [Method] Sprague-Dawley rats were fed with high-fat diet for 9 weeks and on the fourth week-end injected with streptozotocin(STZ) in a dose of 30 mg·kg-1 to set up type 2 diabetic rat model. Put into the mold after fed with high fat diet for 4 weeks.Fasting blood glucose(FBG)was monitored weekly after STZ injection.Urines of normal rats and model rats were col ected at first to ninth week after STZ injection.Triglyceride(TG), total cholesterol(CHO) and plasma insulin(FINS) were measured at 9th week after STZ injection and the rats were sacrificed. The metabolic profiles were analyzed using trimethylsilane(TMCS ) derivatization and gas chromatography-mass spectrometry(GC-MS ). [Results] Compared with the control rats,the FBG,TG and CHO were significantly higher while the FINS was reduced in the model rats. The difference of metabolic profile of the normal group and model group was more and more outstangding as the time went on. Comparative study was applied and fourteen biological markers were different between the normal and model rats.[Conclusion] Metabonomics method with GC-MS was suitable for urinary metabonomics study of type 2 diabete model animals, reflecting the trend of discreting and closing of urinary metabolic profile between the normal group and model group, as wel as inter-normal group and inter-model group, it may reflect a certain extent to the pathological changes of type 2 diabetic rats.
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