Asahi Kamogawa

Plasma thrombomodulin in liver diseases

Thrombomodulin (TM) is an endothelial cell surface membrane protein that binds to thrombin and acts as both a cofactor for protein C activation and an inhibitor of fibrinogenolysis (I). Since TM was discovered in plasma (2), the clinical significance of plasma TM (p-TM) has lately attracted attention. However, alteration of p-TM in liver disease has not yet been reported. Levels of p-TM in liver diseases were measured using a newly developed EIA (3). The levels of p-TM were significantly higher in patients with fulminant hepatitis, decompensated liver cirrhosis, hepatocellular carcinoma (p<0.01) and chronic active hepatitis (p/0.05) than healthy controls, while there was no significant increase in acute hepatitis and compensated liver cirrhosis. (Fig.) Thus the levels of p-TM might be considered to increase as a progression of liver damage, whereas they could be correlated statistically with neither liver function tests nor conventional coagulation-fibrinolytic parameters. The metabolism of p-TMremains obscure. Recently it has been suggested that the levels of p-TMmay increase in patients with collagen disease which involve destruction of vascular endothelial cells. The levels of p-TMare also said to increase in cases of chronic renal failure, in which p-TM is correlated with serum creatinin level. In liver disease, however, no correlation was found between the levels of p-TM and serum creatinin levels. These results indicate that a possible mechanism of increase in p-TM is present in liver disease, which may vascular endothelial cells TM (ng/ml} in damaged liver. ,20

各種生薬メタノールエキスのラットα-Naphthylisothiocyanate(ANIT)肝障害防護効力

Sixty seven methanol extracts of crude drugs were examined for their effects to protect hepatic injury induced by alpha-naphthylisothiocyanate (ANIT) in rats. In terms of the release of intrahepatic enzymes and bilirubin into the serum, 19 extracts were found to suppress the increase in the concentration of serum bilirubin by ANIT. Out of the 19 extracts those of Berchemia Racemosa Caulis, Aurantii Nobilis Pericarpium, Polygoni Avicularis Herba and Gentianae Scabrae Radix, also inhibited the release of several intrahepatic enzymes used as parenchymal injury parameter.

Effect of Interferon Treatment with Chronic Hepatitis C on Serum Level of Thrombomodulin.

C型慢性活動性肝炎22例のIFN治療時の血中TM濃度の推移に関して検討した. IFNは2週もしくは4週間連日投与の後, 週3回隔日投与を22週もしくは20週間行った. IFN治療前の血中TM濃度は健常対照者と比較して有意に高値を示した (p<0.01). IFN投与中の血中TM濃度は投与1週及び2週後に有意に低下した (各々p<0.0001). IFN投与終了時は, R群, NR群とも, 連日投与中に比して, 血中TM濃度は上昇傾向を示し, 治療前と比較して低下を認めなかった. IFN有効群 (R群) での血中TM濃度は, 投与終了6カ月後は治療前値と同程度まで上昇し, 投与終了1年後は健常対照者と同程度に低下した. 無効群(NR群) では投与終了6カ月後の血中TM濃度は, R群に比して有意に高値であった (p<0.05). IFN連日投与中の血中TM濃度の低下は, 肝炎の鎮静化などの病態変化によるものではなく, IFNの血管内皮細胞への直接的な遊離抑制によるものと考えられた. 一方, IFNによるTMの遊離抑制の反作用や, IFNによる血管内皮細胞の傷害が, IFN投与終了後の血中TM濃度上昇に関与している可能性も考えられた.