Effect of atorvastatin on brain edema and its mechanism in rats after focal cerebral ischemia

Objective To observe the dynamic changes of brain edema, tumor necrosis factor-α(TNF-α), aquaporin-4(AQP-4)in focal cerebral ischemia rats and investigate the effect of atorvastatin on the above-mentioned factors. Methods One hundred and eight male SD rats were randomly divided into sham-operated group, model group and treatment group(n=36); furthermore, each group was divided into three subgroups: 1 d group, 3 d group and 7 d group(n=12). Focal cerebral ischemia models in model group and treatment group were induced by left middle cerebral artery occlusion, while rats in the sham-operated group were only separated from blood vessels with no ligation and no inserted line. After succeeded models, the treatment group received gavage administration of atorvastatin(4 mg/[kg · d]), others were given the same dosage of normal saline at the same time. The brain edema was calculated by measuring brain water content via dry-wet method, and the mRNA expressions of TNF-α and AQP-4 were detected by real time-PCR; Western blotting was employed to detect the AQP-4 protein expression. Results At the same observation time, as compared with those in the sham-operated group, the brain water content, TNF-α mRNA expression and AQP-4 mRNA and protein expressions in the model group and treatment group markedly increased(P<0.05); as compared with the model group, treatment group had statistically decreased brain water content, TNF-α mRNA expression and AQP-4 mRNA and protein expressions(P<0.05). Conclusion The brain edema of focal cerebral ischemia rats may be positively correlated to AQP-4 mRNA and protein expressions induced by TNF-α; atorvastatin probably down-regulates AQP-4 mRNA and protein expressions by inhibiting TNF-α to alleviate brain edema and protect brain tissues. Key words: Atorvastatin; Focal cerebral ischemia; Brain edema; Tumor necrosis factor-α; Aquaporins-4