Effect of atorvastatin on angiogenesis of brain tissues in focal cerebral ischemia rats
10.3760/cma.j.issn.1671-8925.2015.04.009
- VernacularTitle:阿托伐他汀对局灶性脑缺血大鼠脑组织血管新生的影响
- Author:
Ting YUE
1
;
Jinlan WANG
;
Zongwen LIU
;
Shuhuan FENG
;
Huijie YANG
Author Information
1. 郑州大学第二附属医院神经内科
- Keywords:
Atorvastatin;
Angiogenesis;
glucose-regulated protein 78;
Caspase-12
- From:
Chinese Journal of Neuromedicine
2015;14(4):473-477
- CountryChina
- Language:Chinese
-
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.
