H Kondo1, T Tani, M Kodama. 1. First Department of Surgery, Shiga University of Medical Science, Shiga, 520-2192, Japan.
Abstract
BACKGROUND: Sepsis is known to be the main cause of multiple organ failure. The liver especially is vulnerable to the stress of infection. In this study, the effects of deletion-type human hepatocyte growth factor (dHGF) on a murine septic model were studied. MATERIALS AND METHODS: Sepsis was induced in male adult Sprague-Dawley rats by cecal ligation and puncture method (CLP). Controls were given a sham operation. Intravenous injection of 1000 micrograms/kg dHGF or the same volume of vehicle was given every 12 h for 3 days before and/or after the CLP from a central vein catheter inserted 1 week prior to the operation. The daily percentage of survival after CLP was followed up for 1 week, and blood samples and liver specimens were collected from the surviving animals 72 h after CLP or sham operation. RESULTS: The survival rate, the degree of liver damage and liver protein synthesis, and coagulation function were all favorable in the dHGF-treated animals compared to the untreated animals. Immunohistochemical staining showed that dHGF prevented the disappearance of thrombomodulin (TM) in liver sinusoid endothelium. CONCLUSIONS: dHGF appears to prevent liver injury caused by disturbance of microcirculation through preservation of TM expression and the antithrombotic function in the endothelium of sinusoids. dHGF also facilitates repair of damaged hepatic tissue by stimulating regeneration of the cells and by preserving hepatic functions such as protein synthesis. dHGF exerts protective effects on even quiescent hepatocytes, but is most effective on injured but competent hepatocytes. Copyright 1999 Academic Press.
BACKGROUND: Sepsis is known to be the main cause of multiple organ failure. The liver especially is vulnerable to the stress of infection. In this study, the effects of deletion-type human hepatocyte growth factor (dHGF) on a murine septic model were studied. MATERIALS AND METHODS: Sepsis was induced in male adult Sprague-Dawley rats by cecal ligation and puncture method (CLP). Controls were given a sham operation. Intravenous injection of 1000 micrograms/kg dHGF or the same volume of vehicle was given every 12 h for 3 days before and/or after the CLP from a central vein catheter inserted 1 week prior to the operation. The daily percentage of survival after CLP was followed up for 1 week, and blood samples and liver specimens were collected from the surviving animals 72 h after CLP or sham operation. RESULTS: The survival rate, the degree of liver damage and liver protein synthesis, and coagulation function were all favorable in the dHGF-treated animals compared to the untreated animals. Immunohistochemical staining showed that dHGF prevented the disappearance of thrombomodulin (TM) in liver sinusoid endothelium. CONCLUSIONS:dHGF appears to prevent liver injury caused by disturbance of microcirculation through preservation of TM expression and the antithrombotic function in the endothelium of sinusoids. dHGF also facilitates repair of damaged hepatic tissue by stimulating regeneration of the cells and by preserving hepatic functions such as protein synthesis. dHGF exerts protective effects on even quiescent hepatocytes, but is most effective on injured but competent hepatocytes. Copyright 1999 Academic Press.