Multivariate modelling with 1H NMR of pleural effusion in murine cerebral malaria
Multivariate modelling with 1H NMR of pleural effusion in murine cerebral malaria
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DOI：
10.1186/1475-2875-10-330
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发表时间：
2011-11-02
期刊：
影响因子：
3
通讯作者：
Sonawat, Haripalsingh M.
中科院分区：
文献类型：
--
作者：
Ghosh, Soumita;Sengupta, Arjun;Sonawat, Haripalsingh M.
背景：脑型疟疾是恶性疟原虫感染的临床表现。虽然脑损伤是脑型疟疾(CM)的主要病理生理并发症，但也有少数病例出现呼吸窘迫、急性肺损伤、胸/胸腔积液。方法：采用主成分分析、正交偏最小二乘分析、多向主成分分析和多元曲线分解等方法对脑疟疾感染小鼠血清和胸腔积液的H-1核磁共振谱进行分析。结果：CM感染的小鼠胸腔积液(PE)发生率为100%，而非脑型感染的高寄生虫血症(NCM/HP)小鼠胸腔积液的发生率为100%。每只CM小鼠的PE和血清样本的1H核磁共振和SDS-PAGE图谱分析在成分方面显示出相似的图谱。对这两类生物体液进行了多变量分析，发现代谢物浓度有显著差异。PE中葡萄糖、肌酸和谷氨酰胺含量较高，血清中血脂含量较高。血清与胸腔积液之间的多元曲线分解显示，CM小鼠PE的变化与血清的变化是一致的。多向主成分分析结果表明，PE中葡萄糖的升高与CM中的血糖呈负相关。结论：本研究首次报道了小鼠脑疟疾期间胸腔积液中代谢产物的特征。提示小鼠心肌中PE代谢物的来源可能是血清。葡萄糖、谷氨酰胺和肌酸等成分的丢失可能会使患者的病情恶化，同时糖酵解、谷氨酰胺分解和肌酸磷酸酶活性增强，这些都是疟疾特有的病理生理特征。
Background: Cerebral malaria is a clinical manifestation of Plasmodium falciparum infection. Although brain damage is the predominant pathophysiological complication of cerebral malaria (CM), respiratory distress, acute lung injury, hydrothorax/ pleural effusion are also observed in several cases. Immunological parameters have been assessed in pleural fluid in murine models; however there are no reports of characterization of metabolites present in pleural effusion.Methods: H-1 NMR of the sera and the pleural effusion of cerebral malaria infected mice were analyzed using principal component analysis, orthogonal partial least square analysis, multiway principal component analysis, and multivariate curve resolution.Results: It has been observed that there was 100% occurrence of pleural effusion (PE) in the mice affected with CM, as opposed to those are non-cerebral and succumbing to hyperparasitaemia (NCM/HP). An analysis of 1H NMR and SDS-PAGE profile of PE and serum samples of each of the CM mice exhibited a similar profile in terms of constituents. Multivariate analysis on these two classes of biofluids was performed and significant differences were detected in concentrations of metabolites. Glucose, creatine and glutamine contents were high in the PE and lipids being high in the sera. Multivariate curve resolution between sera and pleural effusion showed that changes in PE co-varied with that of serum in CM mice. The increase of glucose in PE is negatively correlated to the glucose in serum in CM as obtained from the result of multiway principal component analysis.Conclusions: This study reports for the first time, the characterization of metabolites in pleural effusion formed during murine cerebral malaria. The study indicates that the origin of PE metabolites in murine CM may be the serum. The loss of the components like glucose, glutamine and creatine into the PE may worsen the situation of patients, in conjunction with the enhanced glycolysis, glutaminolysis and increased activity of creatine phophokinase which are already reported characteristic pathophysiological features of malaria.