補(bǔ)骨脂醇提物對(duì)大鼠尿內(nèi)源性代謝產(chǎn)物的影響
本文選題:補(bǔ)骨脂醇提物 + 代謝組學(xué); 參考:《中國(guó)藥理學(xué)與毒理學(xué)雜志》2015年06期
【摘要】:目的基于代謝組學(xué)的方法研究補(bǔ)骨脂醇提物(EEFP)對(duì)正常大鼠尿液內(nèi)源性代謝產(chǎn)物的影響。方法雄性SD大鼠每天1次分別ig給予EEFP 0.54,1.08和1.62 g·kg~(- 1),連續(xù)給藥2周,末次給藥后收集12 h尿液。應(yīng)用超高效液相色譜/四極桿飛行時(shí)間質(zhì)譜(UPLC-Q-TOF-MS)分析尿液,Mass Lynx采集并處理數(shù)據(jù),采用主成分分析(PCA)方法和偏最小二乘判別分析(PLS-DA)方法,分析各組大鼠內(nèi)源性代謝產(chǎn)物的差別,通過正交偏最小二乘法(OPLS-DA)、變量重要程度(VIP)和t檢驗(yàn)篩選潛在生物標(biāo)志物并測(cè)定其相對(duì)含量。結(jié)果 PCA結(jié)果顯示,各組樣本點(diǎn)較好地聚合在一起,各EEFP給藥組與空白對(duì)照組互相完全分離,且與空白對(duì)照組之間的距離隨EEFP給藥劑量的增加而增大;EEFP 0.54,1.08和1.62 g·kg~(- 1)中對(duì)甲酚葡糖苷酸和半乳糖-β-1,4-木糖相對(duì)含量分別為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,明顯低于空白對(duì)照組的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;-;撬帷⑵咸烟撬醿(nèi)酯相對(duì)含量分別為22.4±10.0,47.6±19.1和138.2±18.8,337.3±64.0,明顯高于空白對(duì)照組的2.6±1.6和20.5±6.8(P0.01);EEFP 1.62 g·kg~(- 1)組D-泛酸-L-半胱氨酸相對(duì)含量為74.2±31.5,明顯高于空白對(duì)照組的0.6±0.5(P0.01);隨EEFP給藥劑量的增加,D-泛酸-L-半胱氨酸、5-L-谷氨酰基-;撬岷推咸烟撬醿(nèi)酯含量呈升高的趨勢(shì)(P0.01),半乳糖-β-1,4-木糖和對(duì)甲酚葡糖苷酸含量呈下降的趨勢(shì)(P0.01)。結(jié)論 EEFP給藥2周后,大鼠尿內(nèi)源性物質(zhì)有顯著改變,與能量代謝、酪氨酸和牛磺酸代謝以及葡萄糖代謝有關(guān)。
[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 鹵11.22 鹵2.616.8 鹵6.3,45.9 鹵16.4N 32.6 鹵22.128.0 鹵8.3respectively, which were significantly lower than those in the blank control group (107.0 鹵26.9 and 82.3 鹵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 鹵26.9 and 82.3 鹵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 鹵10.0, 47.6 鹵19.1 and 138.2 鹵18.8337.3 鹵64.0, respectively, which were significantly higher than those of the blank control group (2.6 鹵1.6 and 20.5 鹵6.8p 0.01g / kg 路kg ~ (-1)). The relative content of pantothenic acid-L-cysteine was 74.2 鹵31.5, which was significantly higher than that of the blank control group (0.6 鹵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.
【作者單位】: 中南民族大學(xué)藥學(xué)院生理與藥理教研室;軍事醫(yī)學(xué)科學(xué)院放射與輻射醫(yī)學(xué)研究所;
【基金】:國(guó)家科技重大專項(xiàng)(2014ZX09304307001-003)~~
【分類號(hào)】:R965
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