ANTITHROMBOTIC EFFECT OF RECOMBINANT HUMAN SOLUBLE THROMBOMODULIN ON ENDOTOXIN-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION IN RATS

被引:50
作者
GONDA, Y [1 ]
HIRATA, S [1 ]
SAITOH, K [1 ]
AOKI, Y [1 ]
MOHRI, M [1 ]
GOMI, K [1 ]
SUGIHARA, T [1 ]
KIYOTA, T [1 ]
YAMAMOTO, S [1 ]
ISHIDA, T [1 ]
MARUYAMA, I [1 ]
机构
[1] KAGOSHIMA UNIV, SCH MED, DEPT CLIN LAB MED, KAGOSHIMA 890, JAPAN
关键词
THROMBOMODULIN; DIC; HEPARIN; ENDOTOXIN;
D O I
10.1016/0049-3848(93)90201-X
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thrombomodulin (TM) is an endothelial cell membrane glycoprotein which neutralizes thrombin procoagulant activity and accelerates the thrombin-catalyzed activation of protein C. We expressed recombinant human soluble TM (rhs-TM) in Chinese hamster ovary cells and compared the effects of rhs-TM and heparin on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats. Experimental DIC was induced by a continuous intravenous infusion of endotoxin for four hours. rhs-TM or heparin was infused simultaneously with endotoxin. Treatment with rhs-TM significantly reversed the endotoxin-induced changes in the following parameters: platelet count, fibrinogen level and fibrinogen and fibrin degradation products. Furthermore, glomerular fibrin deposits elevated by endotoxin treatment were reduced by the rhs-TM administration. Heparin showed the similar effects to rhs-TM. Activated partial thromboplastin time (APTT) in rats receiving rhs-TM were slightly longer than APTT in endotoxin-treated rats, but rats receiving heparin had much more prolonged APTT. From these results, we concluded that rhs-TM may be useful for the clinical treatment of DIC while having only minor adverse effects on APTT.
引用
收藏
页码:325 / 335
页数:11
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