Effect of atorvastatin on angiogenesis of brain tissues in focal cerebral ischemia rats / 中华神经医学杂志

ABSTRACT

Objective To investigate the effect ofatorvastatin on angiogenesis of brain tissues in focal cerebral ischemia rats,and explore the corresponding mechanism.Methods Ninety male SD rats were randomly divided into sham-operated group,model group and treatment group (n=30);and then,each group was divided into three subgroups:1 d group,3 d group and 7 d group (n=10).The focal cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO);3 h after MCAO,rats in the treatment group received a gavage of atorvastatin 4 mg/(kg.d),and others were given the same amount of normal saline at corresponding time.The nerve function defects were estimated at 3 h after MCAO and before being killed;the protein expressions of vascular endothelial cell markers CD105 and glucose-regulated protein 78 (GRP78) were analyzed by immunohistochemistry;the vascular endothelial growth factor (VEGF) mRNA expression was analyzed by real time-PCR;the caspase-12 protein expression was analyzed by Western blotting.Results (1) Nerve function defects scores:there was no significantly statistical difference between model group and treatment group at 3 h after MCAO (P＞0.05),but statistical differences at different time points before being killed were noted (P＜0.05).(2) Microvessel density (MVD):at all time points,that of model group was increased as compared with that of sham-operated group,that of treatment group was increased as compared with that of model group,and the differences were all statistically significant (P＜0.05).(3)The VEGF rmRNA expression gradually increased over time;at all time points,the VEGF mRNA expression of model group was significantly higher than that in the sham-operated group,and that of treatment group was significantly higher than that in the model group (P＜0.05).(4)The GRP78 and caspase-12 expressions were gradually decreased over time;at all time points,the GRP78/BiP and caspase-12 expressions in the model group were significantly higher than those in the sham-operated group;those in the treatment group were statistically lower than those in the model group,but obviously higher than those in the sham-operated group (P＜0.05).Conclusion The angiogenesis of brain tissues in MCAO rats is obvious,and atorvastatin can enhance this effect;the mechanism may be that atorvastatin can weaken the endoplasmic reticulum stress,and then,reduce the apoptosis of endothelial cells.