| 研究実績の概要 |
We completed three years of current project. In these three years of project, we used various pharmacological interventions for the treatment of multiple organ dysfunction syndrome (MODS) from early sepsis, some drugs like endothelin blockade, TNF-alpha blockade, protease activated receptor 2 (PAR2) blockade, VEGF receptor antagonist, ultra-short acting beta blocker as therapeutics for MODS in sepsis. Over last several years including the current project we found that endothelin-1 and VEGF play important roles in the pathogenesis of MODS in sepsis with an organ specific roles. In last year of project, we found beta blocker like landiolol has potential roles in reversing sepsis mediated brain and renal injury through the modulation of VEGF and endothelin system. An addition we found landiolol treatment actively arrests acute lung injury in sepsis through suppression of upregulated endothelin system. We also did primary culture of alveolar macrophage and found landiolol inhibited the LPS-induced endothelin upregulation in alveolar macrophage. In another set of experiments, we found diabetes is a strong risk factor for the worsening of MODS in sepsis. Roles of VEGF in MODS became more evident when DM co-existed with sepsis. The downregulation of VEGF in pulmonary and cardiac tissues becomes more prominent when DM is co-existed with sepsis. We also performed clinical research on sepsis with Hokkaido University. We found a potential role of activated protein kinase C in pathogenesis of sepsis with the alteration in VEGF in Japanese sepsis patients.
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