| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Outline of Final Research Achievements |
Inhibition of prolyl hydroxylase (PHD) has been reported to improve the survival rate of mice with endotoxin shock by reduction of the blood lactate level, or and ameliorate cardiac ischemia reperfusion injury, which led us examine the effect of PHD inhibition on Sepsis-induced cardiomyopathy. Adult male mice were intraperitoneally injected with 35 mg/kg of lipopolysaccharide (LPS) and treated with either PHD inhibitor FG-4592 (25 mg/kg) or vehicle by oral gavage. Administration of FG-4592 markedly improved survival rate 7 days after LPS injection, and ameliorated left ventricular dysfunction due to LPS-induced endotoxin shock at 24 hours after LPS injection. Serum level of KYNA was increased upon FG-4592 treatment in mice whereas circulating cytokines levels were not affected. Administration of KYNA promptly improved cardiac dysfunction due to LPS-induced endotoxin shock. Moreover, KYNA administration immediately after LPS reduced mortality on mice with endotoxin shock.
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