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THE ANALYSES OF LIPID MEDIATORS RELATED TO MULTIPLE ORGAN FAILURE AND MECHANISMS THAT PROVOKE BRAIN DAMAGE

与多器官衰竭相关的脂质介质和引起脑损伤的机制的分析

基本信息

批准号：
17390480
负责人：
KOIKE Kaoru
金额：
$ 9.04万
依托单位：
Kyoto University (2006-2007)Tohoku University (2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390480/
关键词：
multiple organ failure lipid mediator intestine brain ischemi lymph Metabonomics nuclear magnetic resonance 再灌流障害

项目摘要

We underwent animal experiments following our original technique. Brain tissue extracts were provided for the study of Nuclear Magnetic Resonance (NMR) metabolomics. Data analyses were performed using "Alice2 for metabolome^<TM>" and "Adome Works/Modelbuilder (Fujitsu Co.)". The water-soluble extract was collected from rat brain after intestinal ischemia-reperfusion (I/R) and used for the 1H-NMR study. (1) The principal component analysis allowed discrimination of different regions, when data from I/R or sham groups were compared on days 1, 3, 5, and 7. The SIMCA method was also able to discriminate each group. (2) The principal component analysis revealed that, in both I/R and sham groups, the data on day.1 distributed in a different region from those on days 3, 5, and 7, suggesting that these metabolic aspects are different from that on day 1. Substances such as ATP, creatinine phosphate, and inorganic phosphate are important for energy metabolism. The idea that 31P-MRS is essential for measuring these substances led us to make an original new surface-coil for 31P-MRS measurements. This coil will allow us to evaluate precursors and degradated endproducts of phospholipids which are main components of cell membranes, and to estimate metabolic changes in the brain tissue. We also analyzed metabolic changes in the rodent intestine and lung before and after hemorrhagic shock. In the intestine, the metabolic state at 120 minutes after resuscitation tended to return to that demonstrated prior to shock. On the other hand, in the lung, the metabolic state at 120 minutes after resuscitation was different from that shown before shock. Using NMR data obtained from the plasma and lymph, we also performed metabolomics analyses in the hemorrhagic shock model. The change in structural elements were clearly shown, when low molecular compounds and lipid-type substances were compared before shock and after resuscitation.

我们按照原来的技术进行了动物实验。脑组织提取物用于核磁共振（NMR）代谢组学研究。使用“Alice 2 for metabolome^<TM>“和“Adome Works/Modelbuilder（Fujitsu Co.）".从肠缺血-再灌注（I/R）后的大鼠脑中收集水溶性提取物，并用于1H-NMR研究。(1)主成分分析允许不同地区的歧视，当I/R或假手术组的数据进行了比较，在第1，3，5和7天。SIMCA方法也能够区分各组。(2)主成分分析显示，在I/R和假手术组中，第1天的数据与第3、5和7天的数据分布在不同的区域，表明这些代谢方面与第1天的数据不同。ATP、磷酸肌酸酐和无机磷酸盐等物质对能量代谢很重要。31 P-MRS对于测量这些物质是必不可少的，这一想法使我们制作了一种用于31 P-MRS测量的新颖的表面线圈。这种线圈将使我们能够评估细胞膜主要成分磷脂的前体和降解终产物，并估计脑组织中的代谢变化。我们还分析了失血性休克前后啮齿动物肠和肺的代谢变化。在肠道中，复苏后120分钟的代谢状态趋于恢复到休克前的水平。另一方面，在肺中，复苏后120分钟的代谢状态与休克前不同。利用从血浆和淋巴中获得的NMR数据，我们还在失血性休克模型中进行了代谢组学分析。在休克前和复苏后比较低分子化合物和脂质类物质时，结构元素的变化被清楚地显示出来。