A 1H nuclear magnetic resonance-based metabonomic approach for grading hepatic encephalopathy and monitoring the effects of therapeutic hypothermia in rats
A 1H nuclear magnetic resonance-based metabonomic approach for grading hepatic encephalopathy and monitoring the effects of therapeutic hypothermia in rats
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DOI：
10.1111/j.1478-3231.2008.01801.x
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发表时间：
2008-09-01
影响因子：
6.7
通讯作者：
Cordoba, Juan
中科院分区：
文献类型：
--
作者：
Barba, Ignasi;Chatauret, Nicolas;Cordoba, Juan
背景：目前还没有很好的生物标志物用于肝性脑病（HE）分级和监测治疗措施的有效性。方法：我们应用(1)基于核磁共振（NMR）的脑代谢组学方法，对肝动脉结扎后（6小时，昏迷前和昏迷阶段），假手术对照组和轻度低温（35℃）6或15小时作为治疗措施后死亡的急性肝衰竭大鼠的脑样本进行分析。结果：偏最小二乘判别分析建立了脑病严重程度评分的分类模型。用低温治疗的动物没有出现脑病的表现，并使用基于核磁共振的代谢组学方法进行相应的分级。与常温动物相比，低温动物的丙氨酸和乳酸水平较低，n -乙酰天冬氨酸和肌醇水平较高。脑干代谢恶化的过程比皮层更快。结论：代谢组学分析能够对HE进行分级，发现区域差异，监测低温的保护作用。这种方法阐明了脑能量代谢和代偿性渗透反应的差异，以解释低温的影响。
Background: There are no good biomarkers for grading hepatic encephalopathy (HE) and monitoring the effectiveness of therapeutic measures. Methods: We applied (1)H nuclear magnetic resonance (NMR)-based metabonomics of brain samples obtained from acute liver failure rats sacrificed after ligation of the hepatic artery (at 6 h, precoma and coma stages), sham-operated controls and mild hypothermia (35 degrees C) for 6 or 15 h as a therapeutic measure. Results: Partial least square discriminant analysis established a classification model that scored the severity of encephalopathy. Animals treated with hypothermia did not develop manifestations of encephalopathy and were graded accordingly using the NMR-based metabonomic approach. Hypothermic animals showed lower levels of alanine and lactate as well as higher levels of N-acetylaspartate and myo-inositol compared with normothermic animals. The course of metabolic deterioration was more rapid in the brainstem than in the cortex. Conclusion: Metabonomic analysis is capable of grading HE, detecting regional differences and monitoring the protective effects of hypothermia. This approach elucidates differences of brain energetic metabolism and compensatory osmotic response to explain the effects of hypothermia.