Full text loading...
薬理と治療
Abstract
Disseminated intravascular coagulation(DIC)associated with sepsis is a serious clinical condition that is characterized by activation of coagulation and widespread microvascular thrombosis resulting in multiple organ failure. In this study, we examined the effects of thrombomodulin alfa(TM alfa)on DIC and organ injury caused by sepsis in a cecal ligation and puncture(CLP)model in rats. In the first study, rats were treated with 3 mg╱kg of TM alfa at 1 hour after CLP operation. After 9 hours of CLP, blood was collected. In the second study, rats were treated with antibiotics:imipenem︱cilastatine sodium(IPM╱CS, 10 mg╱kg)and with or without TM alfa(3 mg╱kg)at 1 hour and 3 hours after CLP, respectively. After 12 hours of CLP, blood was collected. Platelet count(PLT)and plasma level of several parameters including high mobility group box︱1(HMGB ︱1), alanine aminotransferase(ALT)and blood urea nitrogen(BUN)were measured. TM alfa significantly suppressed the changes of PLT, ALT and HMGB ︱1, but not of BUN. The combination therapy with TM alfa and IPM╱CS markedly suppressed changes of PLT, HMGB︱1, ALT and BUN compared with TM alfa monotherapy. These results suggest that TM alfa monotherapy is effective for DIC and organ injury associated with sepsis. Furthermore, the combination therapy with TM alfa and antibiotics exerts further beneficial effects on DIC and organ injury associated with sepsis.
Data & Media loading...