ラット肝硬変モデルにおける血中トロンボモジュリン上昇の意義について

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Thrombomodulin (TM) is one of the vascular endothelial receptors, and it plays a very important role in the anticoagulant system. It exists on the systemic endothelial cells of arteries and veins, and on hepatic sinusoidal endothelial cells. Recent reports indicate that serum TM levels in human increase with chronic hepatitis, liver cirrhosis, dysfunction or failure of the liver, and dysfunction after liver resection. But each report was based on a current condition and only under short observation. We hypothesized that the increase in serum TM levels indicated the injury to sinusoidal endothelial cells, and experimented by using the animal model of cirrhosis induced thioacetamide (TAA) administered to rats. Male Wistar rats weighing 160-200g were used in this experiment. We gave intraperitoneal injections of TAA (200mg/kg) in physiological saline solution (PSS) twice a week. As a control we injected an equal volume of PSS into control rats. After 4 weeks, 8 weeks, 10 weeks and 12 weeks, we examined the blood chemistry and immunohistochemistry of the livers using rabbit anti-human von Willebrand Factor antibodies (Dakopatts; Copenhagen, Denmark), rabbit anti-rat TM polyclonal antibodies (methods informed by the Niigata Institute of Mitsubishi Gas Chemical Company, Japan) and anti-rat hepatic sinusoidal endothelial cell monoclonal antibodies (donated by Sapporo Medical University, School of Medicine, Second Department of Pathology). Results are expressed as mean±SE and analyzed using the paired Student's t-test. Pvalues of .05 or less were regarded as significant. Serum TM levels from the 10 week TAA group (824.4±140.6ng/ml) and 12 week TAA group (838.9±70.0ng/ml) were higher than those of 4 week TAA group (428.1±14.8ng/ml) (p<0.05). Serum hyaluronate levels (HA) of the 12 week TAA group ?(121.4±32.5ng/ml) were higher than those of the 12 week saline group (8.2±3.2ng/ml) (p<0.05). Histological expressions of TM; TM was strongly expressed in hepatic vein endothelial cells and weakly expressed in sinusoidal endothelial cells around central vein in all PSS groups. But the expression of TM in the 12 week TAA group in sinusoidal endothelial cells was stronger than the others. HA increased the degree of capillarization of hepatic sinusoidal endothelial cells. TM increased progressively as the level of injury of the sinusoidal endothelial cells worsened. We conclude that the increase of serum TM levels in hepatic cirrhosis model of rat indicates the dysfunction of sinusoidal endothelial cells.
札幌医科大学の論文
1997-04-01

ラット肝硬変モデルにおける血中トロンボモジュリン上昇の意義について

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