The Experimental Study Of Atorvastatin With Neuroprotective Effects By Upregulating Endothelial Nitric Oxide Synthase Expression In Rat Stroke Model Of Permanent Focal Cerebral Ischemic

Background and Purpose: A growing body of evidence suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, (statins) not only can regulate serum cholesterol level,but can exert anti-inflammatory,antiatherogenic effects.Statins can be mainly used in the acute phase and prophylactic treatment of cardiovascular and cerebrovascular disease . Atrovastatin can regulate serum cholesterol level in poten and secure style.Few studies about its neuroprotective effects and influence on endothelial nitric oxide synthase(eNOS) expression can be found. The present study is mainly an attempt to explore eNOS expression and change tendency under treatment with statins in rats inflicted the permanent occlusion of middle cerebral artery(MCAO),to investigate whether there are differences between pretreatment and treatment with statins , before and after a rodent model of permanent occlusion of middlecerebral artery is well established respectively.Materials and Methods:The models of permanent occlusion of middle cerebral artery were established with the Zea-longa suture method.From 126 adult male SD rats selected,we choosed 18 rats randomly as group A in which sham operations were performed on the rats.The surplus 126 rats were divided into 3 groups at random: group B (36) ,pMCAO operations were performed on the rats;group C (36) ,atrovastatin(10mg/kg) was given to the rats about 2 hours after pMCAO;group D (36) ,atrovastatin(10mg/kg) was given to the rats 7days before pMCAO. Each group was further divided into 3 subgroups: 2d group,3d group,7d group. In addition,6 rats were elected from each subgroup of group B,group C and group D at random,respectively, in order to make immunohistochemical assays and assess the infart volume. According to the Bederson score, The neurological status of each rat was evaluated at 2d,3d,7d post pMCAO by a blinded observer.The infarct volume of each rat was calculated by staining with TTC(2% solution in PBS),and eNOS expression level was observed by immunohistochemical methods.Results: With Bederson score,group B performed significantly difference with group C and group D at 2d,3d,and 7d post pMCAO,but at the same time there is no difference between group C and group D.At 2d,3d,7d, post pMCAO,for infarct volume,there is no difference between group C and group D,but group B performed significantly difference with group C and group D ;With regard to eNOS, at 2d ,3d and 7d post pMCAO, there is no difference between group C and group D; group B performed significantly difference with group C and group D.Conclusion: Atrovastatin can improve the neurologic defict,decrease infarct volume,and increase eNOS expression,which reaches at the peak 3d after pMCAO,almost disappear 7d after pMCAO.AU show that Atrovastatin have therapeutic effect on cerebral infartion.