YAMAOKA Yoshio Kyoto Univ., Graduate School of Medicine, Professor, 医学研究科, 教授 (90089102)
MIYAZAWA Hideaki Akita Univ., School of Medicine, Research Associate, 医学部, 助手 (10323148)
SATO Tsutomu Akita Univ., School of Medicine, Lecturer, 医学部, 講師 (90235367)
TERAJIMA Hiroaki Kyoto Univ., Graduate School of Medicine, Instructor, 医学研究科, 助手 (40314215)
|Budget Amount *help
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2003: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2002: ¥5,100,000 (Direct Cost: ¥5,100,000)
A PDE-III inhibitor, Milrinone, could suppress cAMP degradation in the liver tissue during ischemia-reperfusion. Owing to this effect, serum transaminase increase during reperfusion was effectively suppressed by the Milrinone treatment.
Concerning the mechanism for this beneficial effect, sinusoidal perfusion rate was improved and the leukocytes-endothelial interaction was significantly decreased. Another PDE-III inhibitor, Olprinone, and adenylate cyclase stimulator, NKH477, were also examined. Both of which could suppress the transaminase level during reperfusion. In Olprinone 2 gamma group, ALT release was 1725 IU/l. This value was as half as control. However, the systemic blood pressure was tended to decline below 100 mmHg. The effect of NKH477 on the blood pressure was mild with the dose between 0.1-1.0 gamma, and 0.2 gamma of NKH477 could suppress ALT to 1615 IU/l. When they were simultaneously administered, ALT decreased to 1434 IU/l. Although the power to increase the liver tiss
ue cAMP was greater in 2 gamma Olprinone than 0.2 gamma NKH477, final effects on ALT suppression and blood pressure suggested that NKH477 is better for clinical use than Olprinone. However, further study is necessary.
In the process of stress response, NF-kappaB is one of the most important molecules concerning intracellular information transmission. Since the PDTC is said to suppress the activation of NF-kappaB, we examined the effects of PDTC administration on ischemia-reperfusion injury. Interestingly, PDTC induced HO-1 in the liver tissue and developed remarkable sinusoidal dilatation, probably due to an increase of molecular CO. Consequently, PDTC could produce ischemic tolerance of the liver like PDE-III inhibitors. Since the PDE-III inhibitor had no sinusoidal dilatation effect, signal transduction seemed to be completely different between PDE-III inhibitor and PDTC, although both of which are significant tolerance inducer. These facts indicate the complexity and multiplicity of the molecular information relating to defense system of organism to the stress. Less