| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
To induce sepsis, the cecal slurry (CS) model was applied to 4d-old mouse pups. In brief, adult cecums were harvested, and their contents were diluted with PBS-glycerol for CS stock preparations. HO-1 heterozygote (Het, HO-1+/-) and wild-type (WT) mice were administered CS IP at a dose of 2.0-mg/g (LD40 for WT mice, Fujioka et al, Shock 47:242, 2017), and then monitored for survival. To study the protective role of HO-1 induction, 30-micro mol heme/kg was given to 3d-old pups of both genotypes 24h prior to sepsis induction.
Treatment with 2.0-mg CS/g caused a significantly higher mortality in Het (85.0%) than WT (40.9%, p<0.01) pups. Most importantly, induction of HO-1 by heme significantly reduced mortality in both WT (6.3%) and Het (23.5%) pups. In addition, expression profiles measured using PCR arrays showed significant increases in cytokines in both genotypes 6h post-sepsis induction. This increase was generally attenuated in pups of both genotypes pre-treated with heme.
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