Combined NMR and GC-MS Analyses Revealed Dynamic Metabolic Changes Associated with the Carrageenan-Induced Rat Pleurisy
Combined NMR and GC-MS Analyses Revealed Dynamic Metabolic Changes Associated with the Carrageenan-Induced Rat Pleurisy
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NMR 和 GC-MS 组合分析揭示了与角叉菜胶诱发的大鼠胸膜炎相关的动态代谢变化
DOI：
10.1021/pr400440d
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发表时间：
2013-12-01
影响因子：
4.4
通讯作者：
Tang, Huiru
中科院分区：
文献类型：
--
作者：
Li, Huihui;An, Yanpeng;Tang, Huiru
炎症与多种代谢紊乱、心血管疾病和癌症的发病机制密切相关。为了了解系统对局部炎症的反应，我们使用NMR光谱结合多变量数据分析来分析与角叉菜胶诱导的自限性胸膜炎相关的大鼠血浆和尿液中的动态代谢变化。还使用GC-FID/MS分析了血浆中的脂肪酸，临床化学和组织病理学数据作为补充信息。我们发现在炎症急性期，胸膜炎大鼠血清白蛋白、脂肪酸和脂蛋白水平明显低于对照组，但球蛋白水平较高，胸腔渗出液量较多。角叉菜胶诱导的炎症伴随着显著的代谢改变，包括TCA循环、糖酵解、急性期蛋白的生物合成以及急性期氨基酸、脂肪酸、酮体和胆碱的代谢。胸膜炎的消退过程是不均匀的，在治疗后第6天，观察到两个亚组的炎症大鼠具有不同的代谢特征以及胸膜渗出物的量和胸腺和脾脏的重量。这些亚组之间的代谢差异反映在白蛋白和急性时相蛋白的水平、多个代谢途径恢复正常的程度，包括糖酵解、TCA循环、肠道微生物群功能以及脂质、胆碱和维生素B-3的代谢。这些发现为与角叉菜胶诱导的自限性炎症相关的动态代谢变化提供了一些重要细节，并证明了NMR和GC-FID/MS分析的结合是了解炎症生化方面的有力方法。
Inflammation is closely associated with pathogenesis of various metabolic disorders, cardiovascular diseases, and cancers. To understand the systems responses to localized inflammation, we analyzed the dynamic metabolic changes in rat plasma and urine associated with the carrageenan-induced self-limiting pleurisy using NMR spectroscopy in conjunction with multivariate data analysis. Fatty acids in plasma were also analyzed using GC-FID/MS with the data from clinical chemistry and histopathology as complementary information. We found that in the acute phase of inflammation rats with pleurisy had significantly lower levels in serum albumin, fatty acids, and lipoproteins but higher globulin level and larger quantity of pleural exudate than controls. The carrageenan-induced inflammation was accompanied by significant metabolic alterations involving TCA cycle, glycolysis, biosyntheses of acute phase proteins, and metabolisms of amino acids, fatty acids, ketone bodies, and choline in acute phase. The resolution process of pleurisy was heterogeneous, and two subgroups were observed for the inflammatory rats at day-6 post treatment with different metabolic features together with the quantity of pleural exudate and weights of thymus and spleen. The metabolic differences between these subgroups were reflected in the levels of albumin and acute-phase proteins, the degree of returning to normality for multiple metabolic pathways including glycolysis, TCA cycle, gut microbiota functions, and metabolisms of lipids, choline and vitamin B-3. These findings provided some essential details for the dynamic metabolic changes associated with the carrageenan-induced self-limiting inflammation and demonstrated the combined NMR and GC-FID/MS analysis as a powerful approach for understanding biochemical aspects of inflammation.