論文

基本情報

氏名 加藤 正樹
氏名(カナ) カトウ マサキ
氏名(英語) KATO MASAKI
所属 中村学園大学 栄養科学部 栄養科学科
職名 教授

題名

Microcirculatory disturbance in acute liver injury.

単著・共著の別

 

著者

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

担当区分

 

概要

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). In the low ALT/LDH ratio group, 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 hypercoagulation 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 sinusoidal 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.

発表雑誌等の名称

Experimental and therapeutic medicine

出版者

 

21

6

開始ページ

596

終了ページ

596

発行又は発表の年月

2021-06

査読の有無

 

招待の有無

 

記述言語

英語

掲載種別

研究論文(学術雑誌)

国際・国内誌

国際誌

国際共著

 

ISSN

 

eISSN

 

DOI

10.3892/etm.2021.10028

Cinii Articles ID

 

Cinii Books ID

 

Pubmed ID

 

PubMed Central 記事ID

 

形式

無償ダウンロード

JGlobalID

 

arXiv ID

 

ORCIDのPut Code

 

DBLP ID