Effects Of Simvastatin Preconditioning On Expression Of Bcl-2 And Bax In Rats With Focal Cerebral Ischemia Reperfusion

Objective To investigate the effects of simvastatin preconditioning on apoptosis and expression of Bcl-2 and Bax in rats following focal cerebral ischemia and reperfusion and to explore protective mechanism of simvastatin on the neurons, and providing a new theoretical basis for clinical application.Methods forty-eight adult healthy male SD rats were randomly divided into the control group,sham operation group, Focal Cerebral Ischemia Reperfusion group(FCIR),simvastatin preconditioning group (SSpreconditioning).Before making a model, the rats in the simvastatin preconditioning group were lavaged with simvastatin 20 mg/kg,once a day for 10 consecutive days, and the same volume of normal saline was lavaged for 10 consecutive days in the sham operation and FCIR groups. The middle cerebral artery occlusion reperfusion model was made by the suture method (ischemia for 2 hours, and reperfusion for 4 hours).After that,the animals were neurologically assessed on a 5 Longa point scale,and then beheaded.The volume of infarction were measured by TTC staining,the expression of Bcl-2 and Bax were detected by immunohistochemistry,and the number of the neuron apoptosis was detected by TUNEL.Results1. The cerebral ischemia reperfusion group and simvastatin precongditioning group all have different neurological impairment after cerebral ischemia reperfusion. Compared with the cerebral ischemia reperfusion group,the nuerological scores of the simvastatin preconditioning groups reduced obviously, the two groups were statistically significant (P<0.05).2. After TTC staining the whole brains of the control group and the sham group were red,the right frontal, parietal cortical and striatum of the brains of the cerebral ischemia reperfusion group and simvastatin precongditioning group are white infarcts.Compared with the cerebral ischemic reperfusion group, white infarcts area of the simvastatin precongditioning group decreased, the results were statistically significant (P<0.01).3 Compared with the control group and the sham group, the expression of Bcl-2 and Bax of the cerebral ischemia reperfusion group and the simvastatin precongditioning group are increased (P <0.01), Compared with the cerebral ischemia reperfusion group,the expression of Bcl-2 of the simvastatin precongditioning group is higher(P<0.05), the expression of Bax is lower (P<0.05). while apoptotic cells rarely were seen in the control group and the sham group, apoptotic cells of the cerebral ischemia reperfusion group and the simvastatin precongditioning group increased obviously;Compared with the cerebral ischemia reperfusion group, the simvastatin precongditioning group reduced statistically significant(P<0.01).Conlusion1.Simvastatin preconditioning can decrease neurological scores and contributes to the recovery of limbs after cerebral ischemia reperfusion;2.The effects of simvastatin preconditioning can reduce infarct volume after cerebral ischemia reperfusion;3.Simvastatin preconditioning can increase the expression of Bcl-2, inhibit the expression of Bax and reduce TUNEL positive cells after cerebral ischemia reperfusion,which might be the mechanism of simvastatin neuroprotections.