Co-Investigator(Kenkyū-buntansha) |
HORIO Masaru OSAKA UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (20273633)
SENDA Shoichi KAGAWA MEDICAL UNIVERSITY HOSPITAL, PROFESSOR, 医学部・附属病院, 教授 (30145049)
KIYOMOTO Hideyasu KAGAWA MEDICAL UNIVERSITY, ASSISTANT PROFESSOR, 医学部, 助手 (00304585)
ORITA Yoshimasa KOSHIEN UNIVERSITY, PROFESSOR, 栄養学部, 教授 (70028398)
|
Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥3,100,000 (Direct Cost: ¥3,100,000)
|
Research Abstract |
1) In bovine aortic endothelial cells, 8-iso-PGFィイD22aィエD2, through enhancement of phosphoinositide turnover, stimulated endothelin-1 production and DNA synthesis, the latter of which was partially inhibited by anti endothelin-1 antibody, suggesting an endothelial growth activity of this eicosanoid. 2) Hydrogen peroxide increased 8-iso-PGFィイD22aィエD2, production from cultured rat mesangial cells time- and dose-dependently. This increase was not inhibited by cyclooxygenase inhibitors, such as indomethacin, dexamethazone, varelyl salicylate, or nimesulide, suggesting its producing mechanism independent of cyclooxygenases. Some drugs possessing anti-oxidant action, like vitamin C, vitamin E, sesamine, or probucol, inhibited 8-iso-PGFィイD22aィエD2, production induced by hydrogen peroxide, suggesting the possible application of this system to examine an anti-oxidant action of some drug. 3) The best condition of gene transfer into rat mesangial cells was obtained with 960 μ F at 200V by electroporation method with its efficiency of 2.5% by using Green Fluorescent Protein as an expression marker. 4) In 17 patients who had undertaken direct PTCA performed to treat acute myocardial infarction induced by the occlusion of the proximal portion in the left anterior descending coronary artery, 8-iso-PGF2ィイD22aィエD2 increased by 2.7 fold as an average immediately after the PTCA and gradually decreased to the basal value. This increased lasted longer in those who had undertaken PTCA 12 hours after the onset of their myocardial infarction. In one of them. CPK did not change while 8-iso-PGFィイD22aィエD2 increased markedly immediately after the PTCA. In those who obtained coronary reperfusion only after the PTCA, 8-iso-PGFィイD22aィエD2 increased more greatly and the peak value was inversely correlated to the left ventricular function 3 months after the PTCA, suggesting the role of 8-iso-PGFィイD22aィエD2 in reperfusion-induced myocardial injury.
|