阿托伐他汀对局灶性脑缺血大鼠脑组织血管新生的影响  

Effect of atorvastatin on angiogenesis of brain tissues in focal cerebral ischemia rats

作　　者：乐婷[1] 王金兰[1] 刘宗文[1] 丰树焕 杨会杰[1] 

机构地区：[1]郑州大学第二附属医院神经内科,郑州450000

出　　处：《中华神经医学杂志》2015年第4期473-477,共5页Chinese Journal of Neuromedicine

基　　金：河南省医学科技攻关项目（201303080）;郑州市科技计划项目（科技创新团队）（131PCXTD628）;郑州大学附属第二医院院内基金

摘　　要：目的观察阿托伐他汀对局灶性脑缺血大鼠脑组织血管新生的影响并探讨相应机制。方法选用雄性SD大鼠90只，按照随机数字表法分为假手术组、模型组、治疗组，每组再分为3个亚组：1d组、3d组、7d组，每亚组10只。模型组及治疗组大鼠按照大脑中动脉栓塞法制备局灶性脑缺血模型，假手术组只分离血管，不结扎，不插线。建模后3h，治疗组给予阿托伐他汀钙片4mg／（kg·d）灌胃，其余2组在相应时间给予等量生理盐水灌胃。大鼠建模后3h及给药后1d、3d、7d给予神经功能评分；同时间点采用免疫组化染色法检测新生血管内皮细胞标志物CD105、葡萄糖调节蛋白78（GRP78）：RT-PCR检测血管内皮细胞生长因子（VEGF）mRNA；Western blotting检测凋亡蛋白Caspase-12。结果（1）模型组和治疗组大鼠建模后3h神经功能评分差异无统计学意义（P〉0．05），其余时间点评分差异均有统计学意义（P〈0．05）。（2）各时间点模型组大鼠微血管密度均较假手术组大鼠增加，治疗组大鼠均较模型组大鼠增加，差异均有统计学意义（P〈0．05）。（3）VEGF mRNA表达随时间延长逐渐升高：各时间点模型组大鼠均较假手术组大鼠表达增加，治疗组大鼠均较模型组大鼠表达增加，差异有统计学意义（P〈0．05）。（4）GRP78、Caspase-12表达随时间延长逐渐降低；各时间点模型组大鼠均较假手术组大鼠表达增加，治疗组大鼠均较模型组大鼠表达降低、较假手术组表达增加，差异有统计学意义（P〈0．05）。结论局灶性脑缺血大鼠脑组织血管新生明显，且阿托伐他汀可增强此效应，其机制可能为减弱内质网应激，减少内皮细胞凋亡。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 fimction 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 mRNA 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 mod

关 键 词：阿托伐他汀 血管新生 葡萄糖调节蛋白78 CASPASE-12 

分 类 号：R743.31[医药卫生—神经病学与精神病学]