| Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Outline of Final Research Achievements |
Hepatic IRI provoked significant reduction of ADAMTS13 activity and simultaneous vWF up-regulation. Thus, hepatic microcirculation in KO fell down to 38.4% of the pre-ischemic value, which was significantly lower than in WT (67.5%, p<0.01). Interestingly, rADAMTS13 significantly improved such microcirculatory failure up to 80.2% in KO (p<0.01), and 89.4% in WT (p<0.05). CD42b immunohistochemistry revealed massive platelet aggregation within hepatic sinusoids in KO, which was significantly attenuated by rADAMTS13 not only in KO but also in WT. Consequently, platelet counts (p<0.0001), AST (p=0.0009), ALT (p=0.0015), LDH (p=0.0011) and pro-inflammatory cytokines/chemokines (TNF-a;, IL-1b;, IL-6, IL-10, CXCL-2 and CXCL-10) were all significantly deteriorated in KO, but significantly ameliorated by rADAMTS13 administration. Notably, even in WT, rADAMTS13 significantly improved all such pathologies compared with those without.
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