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)-b...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.展开更多
文摘目的利用代谢组学技术研究急性氰化物中毒大鼠血浆中小分子代谢物的变化,寻找差异代谢物,分析与氰化物中毒相关的代谢途径,进而研究氰化物中毒的机制。方法将健康SD大鼠随机分为空白对照组和实验组(雄性,每组5只),实验组灌胃3.2 mg/kg(1/2LD50)氰化钾溶液建立氰化物急性中毒模型,对照组灌胃等剂纯水,灌胃后分别于45 min,24 h,120 h眼眶静脉采血,通过高效液相色谱-飞行时间质谱采集大鼠血浆代谢谱,根据主成分分析(PCA)、正交偏最小二乘判别分析(OPLS-DA)以及t检验和变异倍数分析筛选差异代谢物,并通过KEGG(Kyoto Encyclopedia of Genes and Genomes)数据库进行代谢通路分析。结果筛选出19个与氰化物中毒相关的差异代谢物,且随时间变化差异代谢物的种类存在差异,主要涉及胆汁分泌、氨基酸代谢等共11条代谢通路。结论可将牛磺胆酸盐和牛磺鹅胆酸盐作为氰化物中毒潜在生物标志物,马尿酸可以作为两者的辅助指标,也可根据差异代谢物的不同进行服药时间的初步推断。氰化物会对机体酶的活性和能量代谢过程产生影响,且可能造成肝脏损伤。
基金Supported by China National Natural Science Foundation Program (No.81160459)
文摘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.