Effects Of Simvastatin Preconditioning On The Expression Of Fas And AIF In Rats Following Focal Cerebral Ischemia And Reperfusion

Objective:To investigate the effects of Simvastatin preconditioning on apoptosis and expression of Fas and AIF in rats following focal cerebral ischemia and reperfusion and to explore protective effects of Simvastatin on the neurons and the mechanism of Simvastatin neuroprotectionsMethod:Established the rat middle celebral artery(MCA) cerebral ischemia/reperfusion(CI/RP) model with suture occlusion technique according to Modified Zea Longa method and then the rats were randomly devided into four groups:control group(n=12),sham-opration group(n=12),vhicle group(n=12) and Simvastatin preconditioning groups ((n=12)),Simvastatin was given by gastrogavage once a day for ten days before focal cerebral ischemia. The middle celebral artlery occlusion model was made by the modified suture method at the eleventh day. After conscionsness, the neurologic impairment evalution scores were record on Longa 5-point scale. The rats were then beheaded after twenty-four hours. The volume of infarction were measured by TTC staining technology, the expression of Fas and AIF were detected by immunohistochemistry technology, and the numbers of the neuron apoptosis were detected by TUNEL technology.Results:1. The neurologic impairment evalution scores:the rats of vehicle group and Simvastatin precongditioning group all have different neurological impairment after CI/RP. Compared with the vehicle group,the nuerological scores of the Simvastatin preconditioning group reduced obviously, showed an significantly difference (P<0.01).2. The volume of infarction,where showed white colour because it was not stained by TTC can be distinguished clearly from the normal brain which showed red colour。Compared with vehicle group,the volume of infarction significantly reduced in Simvastatin preconditioning group (P<0.01).3. Immunohistochemistry technology:Compared with the control group and the sham group, the expression of Fas and AIF and TUNEL positive cells was significantly increased in vehicle and Simvastatin preconditioning group (P<0.01). Compared with vehicle group, the expression of Fas and AIF and TUNEL positive cells was significantly reduced in Simvastatin preconditioning group (P<0.01).Conclusion:1. Simvastatin preconditioning can decrease neurologic impairment evalution scores and contributes to the recovery of limbs after CI/RP.2. The effects of Simvastatin preconditioning can reduce infarction volume after CI/RP. 3. Simvastatin preconditioning can inhibit the expression of Fas and AIF and reduce TUNEL positive cells after CI/RP,which might be the mechanism of Simvastatin neuroprotections.