运用核磁代谢组学技术探讨天丝饮对慢性应激大鼠血清代谢的影响及机制

目的探究天丝饮对慢性应激大鼠血清代谢组学的影响及作用机制。方法采用去势后慢性应激制备大鼠模型,ig天丝饮3.5 g/kg,给药6周后进行水迷宫实验和核磁代谢组学检测。结果水迷宫实验结果显示,与对照组比较,模型组大鼠潜伏距离延长(P<0.01),穿越平台次数减少(P<0.05);与模型组比较,给药组大鼠逃避潜伏距离缩短(P<0.01),穿越平台次数增加。核磁代谢组学结果显示模型组与对照组比较,代谢物丙氨酸、脲基乙内酰脲、精氨酸、肌酸、丙酮酸、丝氨酸含量增加,天冬酰胺酸、肉碱、甘油、N,N-二甲基甘氨酸、N-乙酰谷氨酰胺、苏氨酸、缬氨酸含量减少;葡萄糖、谷氨酰胺、甲基组氨酸含量在不同化学位移表现出不同的变化趋势。天丝饮组大鼠与模型组比较,代谢物精氨酸与丙氨酸均减少;天丝饮组大鼠与对照组比较,代谢物缬氨酸、精氨酸、谷氨酰胺、乙酰乙酸、天冬酰胺酸、赖氨酸、甘油、肉碱、2-氨基-3-羟基丁酸均减少,代谢物脲基乙内酰脲增多。结论天丝饮对慢性应激大鼠血清代谢组学作用机制主要表现在调节氨基酸代谢。

基于核磁代谢组学的酒炙韭菜子温肾助阳作用机制研究

目的:本研究旨在运用代谢组学技术探讨酒炙韭菜子对肾阳虚证模型大鼠的温肾助阳的增效作用机制。方法:将大鼠随机分为模型对照组、生品韭菜子11.1 g/kg组和酒炙韭菜子11.1 g/kg组,大鼠灌胃给予0.5%CMC-Na混悬液或相应药物,连续25 d,给药3 d后,肌肉注射氢化可的松琥珀酸钠25 mg/kg建立肾阳虚证大鼠模型,另设正常对照组。利用与能量代谢相关的药效学指标评价酒炙韭菜子温肾助阳的功效。采用^(1)H-NMR代谢组学技术对血清样本进行分析,寻找与酒炙韭菜子温肾助阳功效相关的差异代谢物,并对其关键代谢通路进行深度解析,阐释其作用机制。结果:与正常对照组大鼠相比,模型对照组大鼠血清中cAMP/cGMP比值明显下降、三酰甘油(TG)含量显著升高,而总胆固醇(TC)、葡萄糖(GLU)含量均显著下降,肝脏组织Na+-K+-ATP酶、Ca^(2+)-Mg^(2+)-ATP酶、琥珀酸脱氢酶(SDH)和乳酸脱氢酶(LDH)活力均显著降低(P<0.01);生品韭菜子对能量代谢指标调节作用较弱,而酒炙韭菜子除cAMP、TG含量明显降低外,上述其余指标均明显升高(P<0.05或P<0.01)。代谢组学结果表明给予酒炙韭菜子11.1 g/kg后,大鼠血清中6种差异代谢物水平与模型对照组比较均具有明显升高或降低,通路分析结果显示其调节作用涉及甘氨酸、丝氨酸和苏氨酸代谢、乙醛酸和二羧酸代谢、牛磺酸和亚牛磺酸代谢等多条作用途径的代谢通路。结论:酒炙韭菜子温肾助阳功效要优于生品韭菜子,其作用机制与调节体内多条代谢通路关系密切。

~1H nuclear magnetic resonance-based metabolomic study on efficacy of Qingrehuatan decoction against abundant phlegm-heat syndrome in young adults with essential hypertension

OBJECTIVE; To observe the influence of Qingrehuatan decoction （QRHT） on serum metabolic profile in young essential hypertension （YEH） patients with abundant phlegm-heat syndrome and provide a basis for treatment with the decoction. METHODS： Twelve male YEH patients were randomly selected and serum samples were collected for examination before and after 4 weeks of thetreatment with QRHT. Twelve healthy males were randomly selected and their serum samples were collected as a control. All serum samples were detected using metabolomic technology with 1H nuclear magnetic resonance. Differences in metabo- lites were studied by principal component analysis and partial least squares-discriminate analysis, which produced scores and Ioadings plots.RESULTS： After 4 weeks of treatment, serum substances could be distinguished between the YEH patients with abundant phlegm-heat syndrome and the control patients. The specific serum endogenous metabolites tended to improve after the treatment. QRHT can appropriately increase the levels of glucose, lactic acid, citric acid, high-density lipoprotein, phosphatidylcholine, glycerophosphate choline, hydroxybutyrate, alanine, and glutamate. QRHT could also decrease the levels of low-density lipoprotein/very low-density lipoprotein, lipids, N-acetyl glycoprotein, and O-acetyl glycoprotein.CONCLUSION： QRHT can effectively ameliorate metabolic disorders in YEH Patients with abundant phlegmheat syndrome. 1H NMR-based metabolo- mic technology can provide an objective basis for the treatment of YEH patients with abundant phlegm-heat syndrome using QRHT.

Nuclear magnetic resonance spectroscopy as a new approach for improvement of early diagnosis and risk stratification of prostate cancer

Prostate cancer （PCa） is the second most common male cancer worldwide and the fifth leading cause of death from cancer in men. Early detection and risk stratification is the most effective way to improve the survival of PCa patients. Current PCa biomarkers lack sufficient sensitivity and specificity to cancer. Metabolite biomarkers are evolving as a new diagnostic tool. This review is aimed to evaluate the potential of metabolite biomarkers for early detection, risk assessment, and monitoring of PCa. Of the 154 identified publications, 27 and 38 were original papers on urine and serum metabolomics, respectively. Nuclear magnetic resonance （NMR） is a promising method for measuring concentrations of metabolites in complex samples with good reproducibility, high sensitivity, and simple sample processing. Especially urine-based NMR metabolomics has the potential to be a cost-efficient method for the early detection of PCa, risk stratification, and monitoring treatment eff^cacy.

An magnetic resonance-based plasma metabonomic investigation on abnormal Savda in different complicated diseases

OBJECTIVE： To provide existence of abnormal potential evidence for the Savda, we assessed host metabonomic responses and dynamic changes oc- curring in various diseases using 1H nuclear mag- netic resonance （NMR）-based metabonomics. METHODS： Plasma samples taken from patients with complicated diseases with abnormal Savda （n= 140, including 35 cases each of diabetes, asthma, breast cancer, and cervical carcinoma） and from healthy controls （n=35） were analyzed by ~H NMR （600 MHz）, and the spectral profiles were analyzed by multivariate analysis using orthogonal projec- tion to latent structure with discriminant analysis. RESULTS： Supervised modeling of the data provid- ed very good discrimination between patients and healthy controls. Compared with ,the healthy controls, the patient groups with different disease con- ditions displayed similar metabolic changes, characterized by lower creatine, creatinine, lactate, and amino acid levels （including isoleucine, leucine, va- line, alanine, and 1-methylhistidine） and higher lip- id levels （very low-density lipoproteins and unsatu- rated lipids）. Additionally, cancer patients （breast and cervical） showed decreased myo-inositol, a-glucose, and 13-glucose, and increased pyruvate and carnitine in plasma. CONCLUSION： The data indicate that decreased ox- idative defense, liver function abnormalities, amino acid deficiencies, and energy metabolism disorders are common characteristics of complicated diseas- es, which may be related to the formation of abnor- mal Savda.