Prevention of venous thrombosis by preoperative glycyrrhizin infusion in a rat model.
BACKGROUND
Glycyrrhizin is an agent with the capacity to bind to selectin molecules expressed on vascular endothelial cells and potentially prevent the adherence of neutrophils to the vascular endothelial surface. It has been found to prevent intravenous thrombus formation.


METHODS
Venous thrombosis was induced in male rats by ligation of the inferior vena cava (IVC) for 6 h. Before the ligation, the study rats were given intravenous injections of glycyrrhizin through the IVC. After 6 h of venous ligation, the rats were sacrificed and the IVC segments were harvested. Thrombus within the IVC was collected to measure the wet weight. Gene expression of P-, L-, and E-selectin was detected by reverse transcriptase polymerase chain reaction using extracts of mRNA from the IVC vein wall. As baseline controls, IVC samples without ligation were harvested immediately after laparotomy. Neutrophil adhesion to the luminal surface of IVC was assessed on histological sections stained with hematoxylin and eosin. Blood samples were collected through the IVC proximal to the ligation after 6 h to estimate activated partial thromboplastin time (APTT) and prothrombin time (PT). To investigate the effect of glycyrrhizin on binding capacity of P-selectin to human neutrophils, real-time biospecific interaction analysis was performed with the Biacore 2000 system.


RESULTS
The mean weight of thrombus in the glycyrrhizintreated group was 12.9 +/- 11.1 mg, which is significantly lower than that of the saline-treated control group (21.3 +/- 12.5 mg). The expression level of P-and L-selectin mRNA in both saline-and glycyrrhizin-treated groups was significantly higher than that of the baseline control. Histological studies of cross sections of IVC showed significantly fewer neutrophils adhering to the luminal surface with glycyrrhizin treatment than in the saline-treated controls. There was no significant difference in the values of coagulation parameters with or without glycyrrhizin treatment. In vitro analysis showed that glycyrrhizin caused a dose-dependent reduction of neutrophils binding to immobilized recombinant P-selectin.


CONCLUSIONS
Preoperative treatment with glycyrrhizin is potentially useful for preventing venous thrombosis by suppressing the adherence of neutrophils to the venous endothelium during the initial phase of thrombus formation without reducing coagulation capacity and the subsequent risk for increased bleeding.
Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Nobuaki
N
Nakata
Yukimi
Y
Kira
Yoriko
Y
Yabunaka
Kunio
K
Takaoka
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D019695:Glycyrrhizic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019087:Selectins / Q000378:metabolism; D014682:Vena Cava, Inferior / Q000378:metabolism / Q000473:pathology; D020246:Venous Thrombosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D019087:Selectins; D019695:Glycyrrhizic Acid