| Co-Investigator(Kenkyū-buntansha) |
OKAZAKI Naoto Tottori University, Faculty of Medicine, Research Associate, 医学部, 助手 (30032204)
MIURA Kazutoyo Tottori University, Faculty of Medicine, Research Associate, 医学部, 助手 (10335507)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
Heat shock protein (HSP) is induced in response to heat stress, and takes an important role in repairing of damaged cell function through molecular chaperon effect. Recently clinically applicable chemical substances have attracted considerable attention, because which induce HSP more safely and effectively. Studies about geranylgeranylacetone (GGA), the HSP inducer is extensively studied mostly in Japan, and shows fruitful reports of inhibitory effect of GGA on ischemia-reperfusion injury of liver, small intestine and heart. As GGA is developed untiulcer drug in our country, and used clinically without a side effect, it is very hopeful for clinical application, if an effect for acute lung injury is confirmed. In the present study, we investigated 1)induction of HSP by GGA, dose dependency, timing of treatment, and organ specificity, then 2)effect of GGA on survival rate of LPS-induced septic shock in rats, and finally 3)effect of GGA on LPS-induced acute lung injury in rats. Present study revealed that GGA induced HSP70 dose- and time- dependently in the liver, kidney and heart. Furthermore, pretreatment of rats with suitable dose of GGA dramatically improved the survival rate of LPS-induced septic shock in rats. Proper induction of HSP70 in the lung tissue was unable to confirm in this study, but we examined the effect of GGA pretreatment on LPS-induced lung injury, and confirmed inhibition of lung injury with GGA. These results suggest that induction of HSP is promising for prevention and treatment for ARDS having high mortality rate. We will advance the research by improving the study method in future.
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