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

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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.