运动对2型糖尿病大鼠血清生物标记物时序性特征的代谢组分析

目的：分析2型糖尿病大鼠在运动干预不同时点的血清生物标记物组合特征。方法：100只SD大鼠，随机选取90只高糖高脂饲料喂养4周，40 mg/kg体重腹腔注射链脲佐菌素（STZ）造模，稳定1周后，71只大鼠成模。最后进入实验共81只大鼠。实施三个时点游泳运动干预（2周、4周和8周）。实验设计共分8组，具体如下：正常对照组（C₀组，n=10）；糖尿病模型对照组（DC₀组，n=10）；糖尿病模型对照2周组（DC₂组，n=10）；糖尿病模型对照4周组（DC₄组，n=10）；糖尿病模型对照8周组（DC₈组，n=9）；糖尿病运动干预2周组（DE₂组，n=11）；糖尿病运动干预4周组（DE₄组，n=10）；糖尿病运动干预8周组（DE₈组，n=11）。采用UPLC/Q-TOF MS技术对大鼠血清进行代谢组学检测，分析运动干预三个时点血清生物标记物的组合特征。结果：依据变化倍数大小排列组合，形成运动干预三个时点的血清生物标记物组合。这些血清生物标记物组合中，大部分差异性物质在不同时点同时出现，但变化倍数有明显不同。2周时点单甘油酸酯的变化倍数最明显，4周时点葡糖酸的变化倍数最明显，4~8周时点二十碳五烯酸、亚麻酸含量可回归至正常水平。结论：2型糖尿病大鼠运动干预不同时点血清生物标记物组合呈现出一定特征。二十碳五烯酸、亚麻酸是运动干预三个时点中上调显著的共同物质，单甘油酸酯、葡糖酸、丙基肉碱、精氨酸、1-磷酸鞘氨醇是三个时点中下调显著的共同物质。

Metabolomics analysis on serum biomarkers timing characteristics of type 2 diabetic rats intervened by exercise

Objective:To analyze the combined features of serum biomarker of exercise-intervened type 2 diabetes mellitus (T2DM) rats at different time point. Methods:Ninety SD rats randomly selected from 100 were fed with high glucose and fat diet for 4 weeks, and then received intraperitoneal injection of streptozotocin(STZ) according to 40 mg/kg by weight; after modeling for one week, Seventy-one rats were successfully modeled among which intervened with swimming at three different time points (2w, 4w and 8w). Eighty-one rats were finally divided into 8 groups as below:Normal control group (C₀,n=10);DM model comparison group (DC₀,n=10); DM model comparison 2w group (DC₂, n=11); DM model comparison 4w group (DC₄, n=10); DM model comparison 8w group (DC₈, n=9); DM exercise intervention 2w group (DE₂, n=11); DM exercise intervention 4w group (DE₄, n=10); DM exercise intervention 8w group (DE₈, n=11).The UPLC/Q-TOF MS technique was used to conduct metabonomics test of serum of rats to analyze the combined features of serum biomarkers under exercise intervention at different time points. Results:According to fold change, we got the biomarker combinations (with 15 specific substances in each combination) of exercise intervention at three time points. In these serum biomarker combinations that were specific at different time points, a majority of metabolites appeared simultaneously at different time points but with obvious difference of fold change. Fold change of monoglyceride(24:6) and gluconic acid were most evident respectively at 2w and 4w intervention time points,Eicosapentaenoic Acid (EPA) andlinolenic acid(LA) contents might approach the normal level at 4~8 time point. Conclusion:Combined features of serum biomarker of exercise-intervened T2DM rats are specific at different time point. Both EPA and LA are common substances significantly up-regulated while MonoglycerideMG(24:6), Gluconic acid, Propionyl-L-carnitine(PLC), Arginine(Arg) and Sphingosine-1-phosphate (SPP) are common substances significantly down-regulated at three time points.