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目的利用基于超高效液相色谱/质谱联用技术(UPLC/MS)的代谢组学平台对2型糖尿病早期大鼠血清进行分析,以期寻找出差异性标志物。方法健康清洁级雄性Wistar大鼠30只,2月龄,体质量(150±15)g。分为对照组和实验组,各15只。实验组适应性喂养1周后,采用高脂饮食和单次腹腔注射55 mg/kg链脲佐菌素(STZ)的方法诱导2型糖尿病动物模型,使用口服葡萄糖耐量实验确认造模成功。于造模成功后1~5周分别收集大鼠血清,并采用高效液相色谱/质谱联用平台分析各标本,再利用主成分分析法(PCA)和正交偏最小二乘-判别分析法(OPLS-DA)对代谢轮廓数据的变异性进行分析,筛选出2型糖尿病大鼠的特征离子,并对它们进行鉴定。结果实验组造模后大鼠血糖升高,随着时间变化,对照组与实验组大鼠之间代谢轮廓差异变大(P<0.05)。血清中乳酸等10种物质相较正常组出现了显著变化(P<0.05),其中乳酸、尿素、甘油、L-异亮氨酸、L-丝氨酸含量显著上升,氨基丙酸、β-羟基丁酸、磷酸、苏氨酸、甘油酸含量降低。结论 STZ法构建的2型糖尿病大鼠血清代谢组学发生明显变化,其中10种物质可能作为糖尿病发生早期的潜在标志物。
OBJECTIVE: To analyze the serum of early type 2 diabetic rats using metabonomics platform based on UPLC / MS (UPLC / MS) in order to find out the differential markers. Methods Thirty healthy male Wistar rats, 2 months old, weighing 150 ± 15 g, were included in this study. Divided into control group and experimental group, each 15. One week after the adaptive feeding in experimental group, type 2 diabetic animal models were induced by high fat diet and single intraperitoneal injection of STZ (55 mg / kg). The oral glucose tolerance test was used to confirm the success of the model. Rat serum was collected 1 to 5 weeks after successful model establishment, and the samples were analyzed by HPLC / MS. The principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to analyze the variability of metabolic profile data. The characteristic ions of type 2 diabetic rats were screened out and identified. Results The blood glucose of model rats increased after experiment, and the difference of metabolic profile between control group and experimental group rats became larger with time (P <0.05). Serum lactic acid and other 10 substances showed significant changes compared with the normal group (P <0.05), including lactic acid, urea, glycerol, L-isoleucine, L-serine content increased significantly, Acid, phosphoric acid, threonine, glyceric acid content decreased. Conclusion Serum metabolomics of STZ-induced T2DM rats have obvious changes, of which 10 kinds of substances may be potential markers for the early stage of diabetes.