Microcirculatory disturbance in acute liver injury

Akifumi Kuwano, Miho Kurokawa, Motoyuki Kohjima, Koji Imoto, Shigeki Tashiro, Hideo Suzuki, Masatake Tanaka, Seiji Okada, Masaki Kato, Yoshihiro Ogawa

研究成果: ジャーナルへの寄稿学術誌査読

抄録

Microcirculatory disturbance is thought to be involved in the pathogenesis of acute liver injury (ALI). The current study examined the pathophysiologic role of hepatic microcirculatory disturbance in patients with ALI and in mouse models of ALI. Using serum aminotransferase (ALT)/lactate dehydrogenase (LDH) ratio as a hypoxic marker, 279 patients with ALI were classified into the low ALT/LDH ratio (ALT/LDH ≤1.5) and high ALT/LDH ratio group(ALT/LDH>1.5).InthelowALT/LDHratiogroup,serum ALT, LDH, fibrinogen degradation products and prothrombin time-international normalized ratio were increased relative to the high ALT/LDH ratio group. Histologically, hepatic expression of tissue factor (TF) and hypoxia-related proteins was enhanced in the low ALT/LDH ratio group, and this was accompanied by sinusoidal fibrin deposition. Sinusoidal hyper- coagulation and intrahepatic hypoxia was also analyzed in two different mouse models of ALI; Concanavalin A (ConA) mice and Galactosamine/tumor necrosis factor (TNF)-α (G/T) mice. Serum ALT/LDH ratio in ConA mice was significantly lower compared with G/T mice. Pimonidazole staining revealed the upregulation of hypoxia-related proteins in ConA mice. Recombinant human soluble thrombomodulin improved liver damage in ConA mice in association with reduced sinu- soidal hypercoagulation and intrahepatic hypoxia. The present study provides evidence that serum ALT/LDH ratio aids in the identification of patients with ALI and intrahepatic hypoxia as a result of microcirculatory disturbance. The results facilitate the improved understanding of the pathogenesis of ALI, thereby offering a novel therapeutic strategy against ALI, which arises from sinusoidal hypercoagulation.

本文言語英語
論文番号596
ジャーナルExperimental and Therapeutic Medicine
21
6
DOI
出版ステータス出版済み - 6月 2021

!!!All Science Journal Classification (ASJC) codes

  • 免疫学および微生物学(その他)
  • 癌研究

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