肉桂水提物对正常大鼠尿液代谢物组的影响

目的:研究肉桂水提物对大鼠尿液中内源性代谢产物的影响。方法:肉桂水提物0.3 g·kg-1大鼠连续ig 30 d,收集0,1,8,15,22,29 d尿样,LC-MS/MS采集样品数据,经主成分分析(PCA),正交信号校正偏最小二乘法判别分析(OSC-PLS-DA)处理数据,结合生物标记物和相关资料,分析肉桂水提物对大鼠内源性代谢产物的影响。结果:肉桂水提物ig 8 d对大鼠尿液中内源性物质的影响最大。与空白组比较,给药组尿样中CPA[18∶1(11Z)/0∶0],Gamma-linolenyl carnitine等物质浓度上升,Deoxyuridine,CerP(d18∶1/22∶0)等物质浓度降低。结论:肉桂水提物能显著影响大鼠体内与基础代谢和细胞信号相关物质的代谢。     

基于NMR技术对Wilson病模型大鼠尿液的代谢组学研究简

目的：以基于核磁共振（NuclearMagneticResonance,NMR）的代谢组学方法对Wilson病（Wilson’sDisea峨WD）铜负荷模型大鼠及正常对照组大鼠的尿液进行研究,分析模型大鼠尿液中代谢物的变化,继而从小分子层面探讨铜过量对机体的损伤机制,以更加清楚的认识本病。方法：28只雄性wistar大鼠,体重（180±20）g,随机被分为模型组（n=14）和健康对照组（n=14）。采用铜负荷法制作wilson病大鼠模型,以NMR技术对大鼠尿液进行检测。采用MestRe—c2．3软件及自编软件对谱图进行手动调相、基线校正和谱峰对齐。对样品进行分段积分．将积分数据归一化后构成数据矩阵,并利用PCA方法对数据矩阵进行统计分析。结果：相对于正常对照组,模型组大鼠尿液醋酸盐（acetate）含量有显著升高,柠檬酸盐（citrate）、苯乙酰甘氨酸（PAG）、琥珀酸盐（succinate）、甲胺（methvlamine）、肌氨酸＋肌氨酸酐（creatine／creatinine）、丙酮酸盐（pyruvate）、二甲基甘氨酸（DMG）、丙氨酸（alanine）含量有所升高,胆碱（choline）、牛磺酸（taurine）含量有所降低。这些发生改变的代谢物可能是潜在的WD铜负荷小分子代谢标志物,可为进一步研究WD的铜过量代谢机制提供参考。     

基于NOESY序列核磁共振技术冠心病心肌缺血血瘀证代谢组学的实验研究

目的 研究Ameriod环所致冠心病心肌缺血血瘀证小型猪的血清代谢物核磁共振谱群的变化。     

过敏性鼻炎患者肺虚感寒证和肾阳亏虚证血清代谢组学研究

[目的]基于气相色谱/质谱(GC/MS)技术的代谢组学方法,分析过敏性鼻炎肺虚感寒证和肾阳亏虚证患者血清中的内源性小分子代谢物变化,为两种中医证型的科学辨证提供依据。[方法]采用GC/MS技术检测过敏性鼻炎患者肺虚感寒证、肾阳亏虚证以及正常人的血清中小分子代谢物,利用SIMCA-P软件进行主成分分析(PCA)及偏最小二乘判别法(PLSA-DA)分析,研究血清中小分子代谢物在各组间的差异。[结果]过敏性鼻炎肺虚感寒证、肾阳亏虚证患者代谢谱具有良好的分离趋势,并与健康人对照组有明显区分。利用商业化的代谢物谱库(如Wiley和NIST质谱库)及本实验室建立的标准品代谢物谱库鉴定了23个具有统计学意义的差异代谢物。在过敏性鼻炎肺虚感寒证和肾阳亏虚证患者中筛选得到了丙氨酸、十四烷酸、十六烷酸、9,12-十八碳二烯酸、9-(Z)-O-十八碳烯酸、十八烷酸6种差异代谢产物。[结论]过敏性鼻炎肺虚感寒证和肾阳亏虚证的代谢差异主要体现在氨基酸代谢和脂肪酸代谢方面,基于GC/MS的代谢组学技术可用于临床不同中医证型的分类研究。     

Metabonomics Techniques and Applications to Pharmaceutical Research & Development

In this review, the background to the approach known as metabonomics is provided, giving a brief historical perspective and summarizing the analytical and statistical techniques used. Some of the major applications of metabonomics relevant to pharmaceutical Research & Development are then reviewed including the study of various influences on metabolism, such as diet, lifestyle, and other environmental factors. The applications of metabonomics in drug safety studies are explained with special reference to the aims and achievements of the Consortium for Metabonomic Toxicology. Next, the role that metabonomics might have in disease diagnosis and therapy monitoring is provided with some examples, and the concept of pharmacometabonomics as a way of predicting an individual's response to treatment is highlighted. Some discussion is given on the strengths and weaknesses, opportunities of, and threats to metabonomics.     

代谢组学研究技术进展

目的介绍代谢组学研究技术的最新进展。方法综合国内外文献报道,介绍当前代谢组学研究中样品制备、仪器分析技术、数据处理方法和结果分析的最新研究概况。结果代谢组学研究技术取得了一定进步,拓宽了代谢组学的应用范围。结论自动化、标准化、整合化和完整化将是代谢组学研究技术的发展方向。     

糖尿病早期大鼠血清代谢轮廓的变化

目的：通过检测1型糖尿病（DM）大鼠血清核磁共振（NMR）谱图的改变来揭示其代谢轮廓的变化。方法：SD大鼠腹腔注射链脲佐菌素（STZ）造成DM模型5周后,收集大鼠的血清并进行NMR分析。结果：DM大鼠相比对照组大鼠的血清代谢轮廓明显不同,D-葡萄糖、甘油、酪氨酸、甘氨酸、胆碱、谷氨酰胺、丙酮酸、3-羟基丁酸、乳酸、丙酮和低密度脂蛋白／极低密度脂蛋白等代谢产物出现了显著变化（P〈0．05或P〈0．01）。结论：代谢组学结果说明DM发生时,糖代谢、氨基酸代谢和脂类代谢出现了紊乱,这为进一步认识DM的发病机制提供了线索。     

代谢组学在中药复方研究中的应用

代谢组学是20世纪90年代中期发展起来的对某一生物或细胞所有低相对分子质量代谢产物进行定性、定量分析的一门新学科。在中药复方研究中,代谢组学方法和技术的应用具有广阔的发展前景,尤其是在中药复方多靶点作用机制、中药复方配伍规律及安全性研究等方面具有重要理论意义和应用价值。代谢组学为中药复方的现代研究提供了强力的技术支撑,将有助于系统、深刻地揭示中药复方的科学内涵,指导中药复方新药研发,更好地传承和发展中医药理论。     

Endogenous and xenobiotic metabolite profiling of liver extracts from SCID and chimeric humanized mice following repeated oral administration of troglitazone

Abstract

1.?Metabonomic analysis, via a combination of untargeted and targeted liquid chromatography-mass spectrometry (LC-MS) and untargeted ¹H NMR spectroscopy-based metabolite profiling, was performed on aqueous (AQ) and organic liver extracts from control (SCID) and chimeric humanized (PXB) mice dosed with troglitazone at 0, 300 and 600?mg/kg/day for seven days.

2.?LC-MS analysis of AQ liver extracts showed a more “human-like” profile for troglitazone metabolites for PXB, compared with SCID, mice.

3.?LC-MS detected differences in endogenous metabolites, particularly lipid species in dosed mice, including elevated triacylglycerols and 1-alkyl,2-acylglycerophosphates as well as lowered diacylglycerophosphocholines and 1-alkyl,2-acylglycerophosphocholines for PXB compared with SCID mouse liver extracts. Following drug administration changes in the relative proportions of the ions for various unsaturated fatty acids were observed for both types of mouse, some of which were specific to PXB or SCID mice.

4.?¹H NMR spectroscopy revealed that AQ PXB mouse liver extracts had elevated amounts of inosine, fumarate, creatine, aspartate, trimethylamine N-oxide, glycerophosphocholine, phosphocholine, choline, glutamine, glutamate, acetate, alanine and lactate relative to SCID mice and decreased histidine, glycogen, α- and β-glucose, taurine, and glutathione. Increased uracil and tyrosine concentrations were detected for PXB mice on troglitazone administration.

5.?Metabonomic profiling thus showed clear differences between humanized and SCID mice, including after administration of troglitazone.