Protective Effect Of Atorvastatin On Brain Slices Injury Induced By H₂O₂ In Vitro

Objective: Oxidative stress is one of the important causes of diabetic central nervous system complications.The model of mouse brain slice injury was established by using hydrogen peroxide（H₂O₂）.The protecte effect and its possible mechanisms of atorvastatin on mouse brain slice injury induced by H₂O₂ were studied.Methods: Brain slices of male C57 mice were divided into four groups: Normal group,model group（2 mM H₂O₂）,lowdose of atorvastatin group（2 mM H₂O₂ + 50 μM atorvastatin）and highdose of atorvastatin group（2 mM H₂O₂ + 100 μM atorvastatin）.The brain slices were stained by 2,3,5-triphenyl tetrazolium chloride（TTC）and the product contents of TTC were determined by spectrophotometer.The activities of dehydrogenase（LDH）and superoxide dismutase（SOD）,and the content of malondialdehyde（MDA）in brain slices were detected by reagent kits.The expressions of Bcl-2,Bax,NF-κB,IL-6 and TNF-α gene were detected by RT-PCR.Results:（1）The red color of slices in model group and atorvastatin group became shallow significantly;TTC staining of brain slices in atorvastatin group was more deepened as compared with model group,and the color of brain slices in highdose atorvastatin was more obvious than that of low-dose atorvastatin.（2）As compared with the normal group,the absorbance of decolorization products in model group decreased obviously（P<0.01）.As compared with the model group,the absorbance of decolorization products in low-dose and high-dose atorvastatin group increased significantly（P<0.05,P<0.01）.（3）The content of LDH in model group was significantly higher than that of the normal group（P<0.01）,Compared with the model group,,the content of LDH was significantly decreased in low-dose and high-dose atorvastatin group.（4）Compared with the normal group,the activity of SOD in the model group was significantly decrease（P<0.01）,while the content of MDA was increased significantly.Compared with the model group,atorvastatin could increase the activity of SOD and decrease the content of MDA.（5）The ratio of Bcl-2/Bax decreased significantly in model group and increased with the pretreatment of atorvastatin（P<0.01）;The expressions of NF-κB,TLR-3 and TNF-α gene were increased significantly in the model group,while the expressions of these genes were declined with the pretreatment of atorvastatin.（6）As compared with the normal group,the content of inflammatory cytokines including NF-κB,IL-6,Cyt-C and TNF-α were significantly increased in the model group.After pretreatment with atorvastatin,the contents of inflammatory cytokines mentioned above were decreased significantly（P<0.01）.Conlusion:（1）H₂O₂ can induce oxidative damage in isolated brain slices,and atorvastatin pretreatment has some protective effects on such injury.（2）Increasing the ratio of apoptosis gene Bcl-2/Bax,inhibition of the inflammatory factor such as NF-κB,IL-6,Cyt-C and TNF-αanddecresed expression of NF-κB,TLR-3 and TNF-α genes,may be one of the mechanisms of atorvastatin against H₂O₂ induced brain slice injury.