LXA₄受容体刺激は脳内出血モデルマウスの運動機能障害を軽減する

抄録

Intracerebral hemorrhage (ICH), a bleeding into the brain parenchyma, is a devastating neurologic disease with the highest mortality among all stroke subtypes. In ICH brain, thrombin induces activation of microglia/macrophages followed by neuroinflammation. Furthermore, ICH leads to infiltration of numerous leukocytes. Recent report shows the arachidonic acid metabolite, leukotriene B₄ (LTB₄), participates pathological progression of ICH (Hijioka et al., 2017). In this study, we focused on lipoxin A₄ (LXA₄), synthesized from arachidonic acid as same as LTB₄. Treatment of murine microglial cell line BV-2 cells with thrombin (30 U/mL) increased mRNA expression level of inducible NO synthase (iNOS) and interleukin-6 (IL-6). Pretreatment with LXA₄ (100 µM) suppressed thrombin-induced increases in iNOS and IL-6 mRNA expression. Moreover, immunocytochemical analysis revealed the translocation of nuclear factor-κB (NF-κB) into the nucleus induced by thrombin, and thrombin-induced nuclear translocation of NF-κB was suppressed by LXA₄. Finally, daily intravenous administration of LXA₄ receptor agonist, BML-111 (1 mg/kg) attenuated the motor dysfunction of mouse model of ICH. These data suggest that LXA₄ may be the novel therapeutic agent for ICH.