Objective To investigate the effect of simvastatin on endothelial cell function in a rat model of sepsis. Methods Ninety-six pathogen-free female Wistar rats aged 4 months weighing 200-250 g were randomly divided into 3 groups (n = 32 each): group sham operation (group Ⅰ ); group sepsis (group Ⅱ )and group simvastatin + sepsis(group Ⅲ ) . Sepsis was induced by cecal ligation and puncture (CLP). In group Ⅲ simvastatin 20 mg/kg was given via a gastric tube once a day for 2 weeks. Blood samples were taken from carotid artery at 3,6, 24 and 48 h ( n = 8 at each time point) for WBC count and measurement of serum E-selectin concentration (by ELISA) . Results CLP significantly increased WBC count and serum E-selectin concentration in group Ⅱ as compared with group Ⅰ . The peak values were reached at 6 h after operation. Simvastatin pretreatment attenuated the sepsis-induced increase in WBC count and serum E-selectin concentration in group Ⅲ. Conclusion Protection of endothelial cell function is involved in the mechanism of treatment of sepsis with simvastatin.

ObjectiveTo investigate the effects of simvastatin preconditioning on the expression of inducible and endothelial nitric oxide synthase ( iNOS,eNOS) in thoracic aorta in a rat model of sepsis.Methods Eighty pathogen-free female Wistar rats aged 4 months weighing 200-250 g were randomly divided into 4 groups:group normal control (group Ⅰ,n =8) ; group sham operation (group Ⅱ,n =8) ; group sepsis (group Ⅲ,n =32) and group simvastatin preconditioning (group Ⅳ,n =32).Sepsis was induced by cecal ligation and puncture (CLP) in groups Ⅲ and Ⅳ.In group Ⅳ simvastatin 20 mg/kg was given via a gastric tube once a day for 2 weeksbefore CLP.The thoracic aorta specimens were taken at 3,6,24 and 48 h after CLP (n =8 at each time point)for detection of iNOS and eNOS protein expression by Western blot analysis.ResultsCLP significantly up-regulated iNOS expression and down-regulated eNOS expression in group Ⅲ as compared with groups Ⅰ and Ⅱ.Simvastatin pretreatment significantly attenuated CLP-induced increase in iNOS expression and decrease in eNOS expression in group Ⅳ as compared with group Ⅲ.ConclusionSimvastatin preconditioning can protect vascular endothelial cells from septic injury by down-regulating iNOS expression and up-regulating eNOS expression in vascular endothelial cells.