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.

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.