The Experimental Study Of Atorvastatin With Neuroprotective Effects By Inhibiting MMP-9 And Upregulating TIMP-1 Expression In Rat Stroke Model Of Focal Cerebral Ischemia/Reperfusion

Background and purpose:A large number of evidence suggest that 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors(statins) can regulate serum cholesterol level,exert anti-inflammatory,antiatherogenic effects.Atorvastatin (atrovastatin) is the role of statins in strong, good safety representative drugs.There are few research at home and abroad about cerebral protective effect on the drug as well as influence on MMP-9 and TIMP-1 expression .The present study is mainly an attempt to explore expression of MMP-9,TIMP-1 and change tendency under pretreatment with statins in rats inflicted the focal cerebral ischemia/reperfusion,influence on protection mechanism of cerebrovascular with interaction of MMP-9 and TIMP-1.Methods: The model of ischemia-reperfusion of middle cerebrai artery were esblished with the Longa method.From 96 adult male SD rats selected,we choosed 16 rats randomly as groupA in which sham operations were performed on the rats. It was divided into 2 subgroups:24h group and 48h group .The surplus 80 rats divided into 2 groups at random: B(40), operations were performed on the rats; group C(40),atrovastatin(5mg/kg) was given to the rats 21days before operations. Each group was divided into 5 subgroups: 3h group,12h group,24h group,48h group and 96h group,. Respectively, all rats were killed at corresponding time. The same day we should executed the test scores of neural behavior,measure ischemic volume with TTC stain, measure expressionsof MMP-9 and TIMP-1 with immunohistochemical SABC method, semi-quantitative for MMP-9mRNA, TIMP-1mRNA analysis with RT-PCR method.Results: With 5-point scale score,group B performed significantly difference with group C at 3h,12h,24h,48h,96h post operations(P<0.05). Measured infarct volume at each time point B, C between the two groups are significantly different (P <0.05). Each time point expression of positive results MMP-9 and TIMP-1, B, C between the two groups are significantly different (P <0.05). Each group relative expressions of MMP-9mRNA and TIMP-1mRNA, there is significant difference between the two groups (P <0.05). After cerebral ischemia 3 hours the pression of MMP-9 were no obvious expressed. The expression of it slightly increased in 12 hours, and in 24 hours it was significantly increased, peaked at 48 hours, decreased in 96 hours . in cerebral ischemia and reperfusion the pression of TIMP-1 peaked in 24 hours, decreased 48 hours.There is linear correlation between two factor.Conclusion: 1.atorvastatin on neurons after ischemia reperfusion has a protective effect.2.inhibiting the expression of MMP-9and upregulating the expression of TIMP-1 is one of the mechanisms of cerebral protection of atorvastatin...