补骨脂醇提物对大鼠尿内源性代谢产物的影响

发布时间：2018-04-17 12:37

本文选题：补骨脂醇提物 + 代谢组学　；参考：《中国药理学与毒理学杂志》2015年06期

【摘要】：目的基于代谢组学的方法研究补骨脂醇提物(EEFP)对正常大鼠尿液内源性代谢产物的影响。方法雄性SD大鼠每天1次分别ig给予EEFP 0.54,1.08和1.62 g·kg~(- 1),连续给药2周,末次给药后收集12 h尿液。应用超高效液相色谱/四极杆飞行时间质谱(UPLC-Q-TOF-MS)分析尿液,Mass Lynx采集并处理数据,采用主成分分析(PCA)方法和偏最小二乘判别分析(PLS-DA)方法,分析各组大鼠内源性代谢产物的差别,通过正交偏最小二乘法(OPLS-DA)、变量重要程度(VIP)和t检验筛选潜在生物标志物并测定其相对含量。结果 PCA结果显示,各组样本点较好地聚合在一起,各EEFP给药组与空白对照组互相完全分离,且与空白对照组之间的距离随EEFP给药剂量的增加而增大;EEFP 0.54,1.08和1.62 g·kg~(- 1)中对甲酚葡糖苷酸和半乳糖-β-1,4-木糖相对含量分别为40.0±11.2,2.7±2.6,16.8±6.3和45.9±16.4,32.6±22.1,8.0±8.3,明显低于空白对照组的107.0±26.9和82.3±13.6(P0.01);EEFP 1.08和1.62 g·kg~(- 1)中5-L-谷氨酰基-牛磺酸、葡萄糖酸内酯相对含量分别为22.4±10.0,47.6±19.1和138.2±18.8,337.3±64.0,明显高于空白对照组的2.6±1.6和20.5±6.8(P0.01);EEFP 1.62 g·kg~(- 1)组D-泛酸-L-半胱氨酸相对含量为74.2±31.5,明显高于空白对照组的0.6±0.5(P0.01);随EEFP给药剂量的增加,D-泛酸-L-半胱氨酸、5-L-谷氨酰基-牛磺酸和葡萄糖酸内酯含量呈升高的趋势(P0.01),半乳糖-β-1,4-木糖和对甲酚葡糖苷酸含量呈下降的趋势(P0.01)。结论 EEFP给药2周后,大鼠尿内源性物质有显著改变,与能量代谢、酪氨酸和牛磺酸代谢以及葡萄糖代谢有关。
[Abstract]:Objective to study the effect of EEFP1 on urinary endogenous metabolites in normal rats.Methods male Sprague-Dawley rats were given EEFP 0.54g / kg 1.08 and 1.62 g / kg / day intravenously for 2 weeks respectively. Urine samples were collected for 12 hours after the last administration.UPLC-Q-TOF-MS was used to analyze the data collected and processed in urine mass Lynx. The difference of endogenous metabolites was analyzed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA).The potential biomarkers were screened by orthogonal partial least square method (OPLS-DAA) and t-test, and the relative content of the potential biomarkers was determined.Results the results of PCA showed that the sample points of each group were well aggregated, and each EEFP group was completely separated from the blank control group.The relative contents of p-cresol glucuronide and galactosyl- 尾 -1-xylose in the control group were 40.0 卤11.22 卤2.616.8 卤6.3,45.9 卤16.4N 32.6 卤22.128.0 卤8.3respectively, which were significantly lower than those in the blank control group (107.0 卤26.9 and 82.3 卤13.6p 0.01P 0.01f1.08, respectively), which increased with the increase of the dosage of EEFP in the control group, and the relative contents of p-cresol glucuronide and 尾 -galactose-4-xylose in the blank control group were significantly lower than those in the blank control group (107.0 卤26.9 and 82.3 卤13.6g / kg 路kg ~ (-1)), respectively.In 1.62 g kg-1), 5-L-glutamyl-taurine,The relative contents of glucuronolactone were 22.4 卤10.0, 47.6 卤19.1 and 138.2 卤18.8337.3 卤64.0, respectively, which were significantly higher than those of the blank control group (2.6 卤1.6 and 20.5 卤6.8p 0.01g / kg 路kg ~ (-1)). The relative content of pantothenic acid-L-cysteine was 74.2 卤31.5, which was significantly higher than that of the blank control group (0.6 卤0.5) P0.01a;The contents of -L-cysteine, 5-L-glutamyl-taurine and gluconate lactone increased, while the contents of galactos- 尾 -1-buta-4-xylose and p-cresol glucuronide decreased.Conclusion after 2 weeks of administration of EEFP, urinary endogenous substances were significantly changed in rats, which were related to energy metabolism, tyrosine and taurine metabolism and glucose metabolism.
【作者单位】：中南民族大学药学院生理与药理教研室;军事医学科学院放射与辐射医学研究所;
【基金】：国家科技重大专项(2014ZX09304307001-003)~~
【分类号】：R965

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