坎地沙坦预处理对大鼠脑缺血再灌注损伤的血管保护作用  

Blood vessel protection effect of pretreatment with candesartan on cerebral ischemia -reperfusion in rats

作　　者：聂亚雄[1] 朱云龙[1] 黄如训[2] 尹剑[1] 高帆[1] 罗焱[1] 游咏[1] 

机构地区：[1]南华大学附属第一医院神经内科,湖南衡阳421001 [2]中山大学附属第一医院神经内科,广东广州510120

出　　处：《中风与神经疾病杂志》2010年第7期589-593,共5页Journal of Apoplexy and Nervous Diseases

基　　金：湖南省自然科学基金(08JJ3036)

摘　　要：目的探讨坎地沙坦预处理大鼠局灶性脑缺血后缺血区脑组织中内皮型一氧化氮合酶(eNOS)、血管内皮生长因子(VEGF)的表达,研究坎地沙坦的脑血管保护作用。方法 64只雄性SD大鼠,随机分为假手术组、缺血再灌注组、坎地沙坦低剂量组(0.1mg/kg.d)、坎地沙坦高剂量组(1mg/kg.d),每组16只,各组又随机分为缺血2h再灌注24h和72h两个亚组(每组8只)。灌胃4w后,采用大脑中动脉线栓法制备局灶性脑缺血模型,术前测量血压,术后24h监测缺血区大脑中动脉脑血流变化,再灌注24h、72h分别检查神经功能评分,断头取脑后TTC染色,免疫组化检测缺血区脑组织血管内皮eNOS、VEGF的蛋白表达。结果与缺血再灌注组比较,坎地沙坦低剂量组与高剂量组再灌注24h、72h神经功能评分均有好转(P<0.05),脑梗死面积明显减少(P<0.05),两组之间比较差异无统计学意义(P>0.05)。坎地沙坦高剂量组在服药后2w血压明显下降,维持在85mmHg,小剂量组无降压作用。缺血2h后,缺血再灌注组右侧大脑中动脉缺血区血流量下降为32%±3%,坎地沙坦低剂量组及高剂量组血流量分别为55%±5%、64%±7%。eNOS和VEGF阳性表达主要分布于梗死灶周围的血管内皮细胞。eNOS在坎地沙坦低剂量和高剂量组24h达到高峰(P<0.05),随后逐渐下降,VEGF随着时间延长表达进一步增加,再灌注72h达到最大。结论坎地沙坦通过改善缺血区脑血流量,上调缺血区eNOS及VEGF的表达,达到改善神经功能评分及减少脑梗死面积的目的。VEGF和eNOS可能成为缺血性脑卒中重要的保护靶点。Objective To explore the protective effect of cerebral vessels in the ischemia region of focal cerebral ischemia in rats by pretreatment with candesartan through examing the change and relationship between eNOS and VEGF. Methods 64 male SD rats were randomly divided into sham operation group,ischemia-reperfusion group,candesartan low-dose group （0.1mg/kg·d） and candesartan high dose group （1mg/kg·d）. There were 16 rats in every group,each group was randomly divided into two sub-groups （n=8）：reperfusion for 24h or 72h. Intragastric administration for 4 weeks. Focal cerebral ischemia model was established via middle cerebral artery occlusion （MCAO） with the intraluminal filament method,blood pressure of each rat before operation was measured. Cerebral blood flow of ischemic region was quantified by laser-Doppler flowmetry after MCAO,24h and 72h after MCAO. Each rat was examined for neurological scores,then rats were decapitated,the brains were rapidly removed with TTC staining,immunohistochemical detection protein expression of eNOS,VEGF in vascular endothelial cell of ischemic cerebral. Results Compared with ischemia-reperfusion group,candesartan low-dose group and high-dose group at 24h and 72h after reperfusion Showed improved neurological scores （P〈0.05） and significantly reduced infarct sizes （P〈0.05）. There was no significant difference between the two groups （P〈0.05）. Candesartan high-dose group showed significantly decreased blood pressure after 2 weeks,maintained at 85mmHg;while low-dose group had not antihypertensive effect. After 2h occlusion,in ischemia-reperfusion group,cerebral blood flow of the ischemic region in right middle cerebral artery decreased to 32%±3%,while in candesartan low-dose group and high-dose group,increased to 55%±5% and 64%±7% respectively （P〈0.05）. eNOS and VEGF were expressed mainly in the vascular endothelial cells of infarct peripheral tissues. eNOS in the candesartan low-dose and high-dose group peaked at 24h after reperfusion �

关 键 词：坎地沙坦 脑缺血再灌注 血管内皮生长因子 内皮型一氧化氮合酶 

分 类 号：R743.3[医药卫生—神经病学与精神病学]