Protective Effect of Simvastatin on Myocardium in Septic Rats

Objective To investigate the protective effect of simvastatin on myocardium in septic rats and its possible mechanism of action.Methods Thirty 4-week-old male Wistar rats were randomly divided into three groups.Laparotomy and manipulation of the cecum were performed in sham operated group.Sepsis was induced by cecal ligation and puncture(CLP) in CLP group.Intravenous injection with simvastatin(20 mg·kg-1) dissolved in 10% dimethylsulfoxide(DMSO,1 mL·kg-1) and normal saline(2 mL·kg-1) was performed after CLP in simvastatin group.Rats in sham operated group and CLP group were injected with 3 mL·kg-1 of normal saline.Six rats were sacrificed in each group at 5 hours after CLP and in CLP group and simvastatin group at 20 hours after CLP.The blood and myocardial samples were collected,and the levels of serum CKMB,myocardial TNF-α and myocardial NO were measured.Pathological lesions in myocardial tissue was observed by light microscope and the expression of TLR-4 protein was determined by immunohistochemistry.Results In CLP group,myocardial tissue was seriously injured,and the expression of TLR4 was obviously detected.Compared with sham operated group,the levels of CKMB,TNF-α and NO significantly increased in sham operated group(P0.01).The maximum levels of CKMB,TNF-α and TLR-4 expression were observed at 5 hours after CLP,while the maximum NO levels were observed at 20 hours after CLP.Compared with CLP group,myocardial damage was reduced and the levels of CKMB,TNF-α,NO and TLR-4 expression were decreased by simvastatin(P0.01).Conclusion The protective effect of simvastatin on myocardial damage in septic rats may be mediated by a mechanism involving the inhibition of TLR-4 signaling pathway and the reduction of TNF-α and NO over-expression.