| Co-Investigator(Kenkyū-buntansha) |
NAITO Tokio Kyushu Univ.Fac.Med.Research fellow, 医学部, 医員
IGIMI Hirotsune ShinogiBiomedical Laboratory Manager, シオノギバイオメデイカルラボラトリ, 所長
HAMASAKI Naotaka Kyushu Univ.Fac.Med.Professor, 医学部, 教授 (00091265)
CHIJIIWA Kazuo Kyushu Univ.Fac.Med.Lecturer, 医学部, 講師 (90179945)
亀岡 宣久 九州大学, 医学部, 医員
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
Phsophoeneolpyruvate (PEP) is a high energy metabolite in the final step of glycolysis. PEP is converted into pyruvate by pyruvate kinase. One molecule of adenosine triphosphate (ATP) is generate from one molecule of PEP.The aim of this study was to examine the effects of PEP on hepatic energy metabolism at an early phase after ischemia and reperfusion in rats. Male Wister rats (250-350g) were divided into two groups ; after two 15-min periods of ischemia with 2 min reperfusion in between, either PEP or glucose solution (400mmol/liter, pH7.4) was infused into the portal vein (2.5ml/300g body wt/5min). Before and 0,5,10 and 30 min after ischemia, arterial blood and liver tissue were collected fo analyzes. Results : During the two ischemic periods, ATP and total adenine nucleotide (TAN) of the liver decreased from 9.10(]SY.+-。[)0.50 and 14.06(]SY.+-。[)0.29 to 0.99(]SY.+-。[)0.50 and 10.86(]SY.+-。[)0.42mmole/g liver, respectively (P<0.05), while adenosine monophoshate (AMP) increased from
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1.18(]SY.+-。[)0.15 to 8.47(]SY.+-。[)0.6mmole/g liver (P<0.05). Hepatic energy charge (EC) significantly decreased from 0.78(]SY.+-。[)0.02 to 0.16(]SY.+-。[)0.03 (P<0.005). Serum concentration of pyruvate and lactate were elevated from 1.18(]SY.+-。[)0.15 and 18. (]SY.+-。[)0.52 to 3.29(]SY.+-。[)0.52 and 72.6(]SY.+-。[)4.8mg/dl, respectively (P<0.05). After a 5-min infusion of PEP or glucose solution, the ATP concentration was significantly higher in the PEP group than in the glucose grc (4.08(]SY.+-。[)0.58mumole/g liver vs 2.20(]SY.+-。[)0.45mumole/g liver, P<0.01), whereas AMP concentration was significantly lower in the PEP group than in the glucose group (4.26(]SY.+-。[)0.66mumole/g liver vs 7.02(]SY.+-。[)0.71mumole/g liver, P<0.01). EC in the PEP group was significantly higher than that in the PEP group (0.493 : 0.051 vs 0.293(]SY.+-。[)0.042, P<0.01). Ten minutes after ischemia, the ATP,TAN,and EC level were still higher in the PEP group than in the glucose group, the difference did not reach statistical significance. A min after ischemia, these values became similar in both groups. At 5,10, and 30 min after ischemia, serum pyruvate concentrations were higher in the PEP group than in the glucose group. Conclusion : The findings suggest that PEP recover hepatic energy from liver cell damage at an early phase after ischmeia reperfusion by prompt ATP production through the degradation of PEP into pyruvate in the liver. Less
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