摘要
目的对肥胖抵抗大鼠尿液进行代谢组学分析,研究高糖高脂饮食对非肥胖型代谢紊乱的影响,探讨非肥胖型2型糖尿病的发病机制。方法建立肥胖抵抗大鼠模型,取静脉血,测其生化指标,同时对尿液进行气相色谱-质谱分析,得到的数据进行代谢组学分析。结果除羰基戊二酸(RSD=11.77%)外,其他14种代谢物的相对标准偏差(RSD)均在10%以内,R2Y和Q2值分别为0.929和0.905;与对照组相比,肥胖抵抗组大鼠尿液中能量代谢过程的相关代谢物羟基乙酸、苏氨酸、丝氨酸、丁二酸、延胡索酸、2,3-二羟基-丁酸、苹果酸、羰基戊二酸减少,同时与肠道菌群代谢相关的代谢物对羟基苯甲酸、葡萄糖醇、反式乌头酸、果糖、葡萄糖、肌醇含量也明显减少。结论饮食干预16周之后,肥胖抵抗组大鼠能量代谢过程中的主要代谢物发生异常,基于GC-MS的代谢组学分析方法能较为全面的反应能量代谢状况,发现差异代谢物,可用于非肥胖型2型糖尿病发病机制的研究。
Objective A GC - MS based methodology was developed in order to investigate the differences of the metabolite profiles of the urine from the Wistar rats after 16 weeks of high - fat and high - sugar feeding. Methods A obesity resistant rat model was con- structed and the biochemical criteria in dnding the level of fasting plasma glucose, triglyceride, total cholesterol,high density lipoprotein and lower density lipoprotein were analyzed. The metabolites in the urine were exhaustively separated and detected by GC - MS. Multiva- riate metabonomics analysis was performed after peak alignment. Collected data were transformed, the peak alignment between different chromatograms was performed to generate the peak table, then orthogonal signal correction filtered partial least - squares discriminate anal-ysis （OSC -PLS -DA） was carried out to model the data（ R2 = 0. 929, Q2 = 0. 905） and discover metabolites with a significant concentra- tion change in the obesity resistant rats. Results Compared with the controls, the obesity resistant rats showed lower levels of glycolic acid, serine, threonine, butane diacid, fnmaric acid, 2,3 - dihydroxy - butyric acid, malic acid, carbonyl glutarie acid, p - hydroxy- benzoic acid, p- hydroxyphenyl acetic acid, glucitol, trans -aconitic acid, fructose, glucose, inositol, meantime the serum sugar （4.19±0.47 vs 6.48 ± 1.16） and insuline（4.29 ± 0.58 vs 6.20 ± 1.35） incressed. Conclusion After 16 weeks, the obesity resistant rats showed clear metabolic dysfunctions of glucose, lipid and amino acid. The results showed that GC - MS based metabonomics analysis could be helpful for understanding the mechanism of the non - obese metabolic disease,especially type 2 diabetes mellitus.
出处
《医学研究杂志》
2012年第12期95-99,共5页
Journal of Medical Research
