不同病程的结核病患者的血浆代谢组学研究

Plasma Metabonomics in Tuberculosis Patients at Different Stages

结核病(tuberculosis,TB)是第二大由单一病原菌感染引起的致死性疾病,致死率仅次于艾滋病.与疾病进展相关的代谢标志物的发现有利于病情的防治,而代谢组学研究则是发现代谢标志物的重要手段之一.目前与TB病人相关的代谢组学研究还不多.该文利用基于核磁共振氢谱(1H NMR)的代谢组学技术,对不同病情程度TB患者的血浆代谢组进行了研究.正交偏最小二乘法判别分析(OPLS-DA)结果显示TB各组与健康对照组均可明显分离.统计分析发现,缬氨酸、丙氨酸、肌酸和3-羟基丁酸等代谢物在TB各组含量普遍高于对照组;乳酸、丙酮酸、N-乙酰糖蛋白、亮氨酸和谷氨酸等代谢物在疾病进展过程中呈逐渐增加的趋势,而三羧酸(tricartexylic acid,TCA)循环的中间产物——柠檬酸则呈逐渐降低的趋势,表明了代谢紊乱随疾病的逐渐变化过程.这些差异代谢物的变化表明TB患者体内能量代谢与糖酵解增强、脂肪酸生酮作用增强、TCA循环受阻、氨基酸代谢紊乱.

Tuberculosis（TB） is the second largest infectious disease caused by a single pathogen leading to mortality, only after AIDS. Discovery of biomarkers associated with disease progression is vital for TB screening and control. Metabonomics is among the most useful tools for this purpose. A few metabonomic studies on TB patients have been published. In this study, the plasma samples of TB patients with varying severity were studied by 1H NMR based metabonomics. Orthogonal partial least squares-discriminant analysis（OPLS-DA） models showed that TB patients at different stages and healthy controls could be differentiated by their plasma metabolic profiles. It was found that the TB groups had significantly higher levels of valine, alanine, creatine, and 3-hydroxybutyrate, relative to the healthy controls. In the TB patients, the levels of lactate, pyruvate, N-acetyl glycoprotein, leucine and glutamate increased gradually with disease progression, while the level of citrate, a tricarboxylic acid（TCA） cycle intermediate, decreased with disease progression. The plasma metabolic profile changes indicated increased energy metabolism and glycolysis, enhanced ketogenesis of fatty acid, reduced TCA cycle, and disordered amino acid metabolism in the TB patients.