坎地沙坦预处理对脑缺血再灌注大鼠血管内皮生长因子表达的影响  

Effect of pretreatment with candesartan on the expression of vascular endothelial growth factor after cerebral ischemia-reperfusion in rats

作　　者：刘福中 朱云龙[2] 聂亚雄[2] 

机构地区：[1]湘潭市中心医院神经内科,411000 [2]南华大学附属第一医院神经内科,衡阳421001

出　　处：《国际脑血管病杂志》2010年第9期658-663,共6页International Journal of Cerebrovascular Diseases

摘　　要：目的 探讨坎地沙坦预处理对脑缺血大鼠的血管保护作用.方法 48只雄性SpragurDawley大鼠,随机分为假手术组、缺血再灌注组以及坎地沙坦小剂量组[0.1 mg/（kg·d）]和大剂量组[1 mg/（kg·d）],每组12只 各组又随机分为缺血2 h后再灌注24 h和再灌注72 h亚组（每组6只）.药物灌胃4周后,采用线栓法制备大脑中动脉闭塞模型,术前测量血压,分别在再灌注24 h和72 h后进行神经功能评分,然后断头取脑,采用2,3,5-氯化三苯基四氮唑染色测定脑梗死体积,通过免疫组化染色和Western印迹分析检测缺血区脑组织血管内皮生长因子（vascular endothelial growth factor,VEGF）蛋白表达.结果 坎地沙坦小剂量组和大剂量组再灌注24 h和72 h神经功能评分均显著优于缺血再灌注组（P分别为0.008和0.001）,脑梗死体积显著缩小（P分别为0.010和0.000）.坎地沙坦大剂量组在干预后第2周血压明显下降,小剂量组无明显降压作用.VEGF阳性表达主要分布于梗死灶周围区血管内皮细胞,其表达随时间推移进一步上调,再灌注72 h达峰值.Western印迹分析与免疫组化染色结果一致.结论 坎地沙坦可能通过上调缺血区VEGF表达缩小脑梗死体积,改善神经功能评分.Objective To investigate the vascular protective effect of pretreatment with candesartan on cerebral ischemia in rats.Methods Forty-eight male Sprague Dawley rats were randomly divided into sham operation,ischemia-reperfusion,low-dose candesartan group was randomly redivided into reperfusion 24 h and 72 h subgroups （n = 6）.A model of middle cerebral artery occlusion was induced by intraluminal suture method after 4 weeks of drug gavage.Blood pressure was measured preoperatively.The neurological scores were performed after 24 and 72 hours of reperfusion.Then the rats were decapitated and the brains were removed.The infarct volume was measured using 2,3,5-triphenyltetrazolium chloride staining.The expression of vascular endothelial growth factor （VEGF） protein in ischemic regions was detected by immunohistochemical staining and Western blot analysis.Results The neurological scores of the low-dose and high-dose candesartan groups at 24 and 72 hours after reperfusion were significantly better than those of the ischemia-reperfusion group （P = 0.008and 0.001,respectively）,and the infarct volume was reduced significantly （P=0.010 and 0.000,respectively）.At the second week after medication,the blood pressure was decreased significantly in the high-dose candesartan group,and there was no significant antihypertensive effect in the low-dose candesartan group.The positive expression of VEGF mainly distributed in the vascular endothelial cells around the infarcts.Its expression was further upregulated with the time.It reached the peak after 72-hour reperfusion.The result of Western blot analysis was consistent with that of immunohistochemical staining.Conclusions Candesartan may reduce the infarct volume by upregulating the expression of VEGF in the ischemic region and improve the neurological score.

关 键 词：坎地沙坦 脑缺血 再灌注损伤 血管内皮生长因子 大鼠 

分 类 号：R74[医药卫生—神经病学与精神病学] R9[医药卫生—临床医学]