国际脑血管病杂志
國際腦血管病雜誌
국제뇌혈관병잡지
INTERNATIONAL JOURNAL OF CEREBROVASCULAR DISEASES
2010年
9期
658-663
,共6页
坎地沙坦%脑缺血%再灌注损伤%血管内皮生长因子%大鼠
坎地沙坦%腦缺血%再灌註損傷%血管內皮生長因子%大鼠
감지사탄%뇌결혈%재관주손상%혈관내피생장인자%대서
Candesartan%Brain ischemia%Reperfusion injury%Vascular endothelial growth factor%Rats
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.
目的 探討坎地沙坦預處理對腦缺血大鼠的血管保護作用.方法 48隻雄性SpragurDawley大鼠,隨機分為假手術組、缺血再灌註組以及坎地沙坦小劑量組[0.1 mg/(kg·d)]和大劑量組[1 mg/(kg·d)],每組12隻;各組又隨機分為缺血2 h後再灌註24 h和再灌註72 h亞組(每組6隻).藥物灌胃4週後,採用線栓法製備大腦中動脈閉塞模型,術前測量血壓,分彆在再灌註24 h和72 h後進行神經功能評分,然後斷頭取腦,採用2,3,5-氯化三苯基四氮唑染色測定腦梗死體積,通過免疫組化染色和Western印跡分析檢測缺血區腦組織血管內皮生長因子(vascular endothelial growth factor,VEGF)蛋白錶達.結果 坎地沙坦小劑量組和大劑量組再灌註24 h和72 h神經功能評分均顯著優于缺血再灌註組(P分彆為0.008和0.001),腦梗死體積顯著縮小(P分彆為0.010和0.000).坎地沙坦大劑量組在榦預後第2週血壓明顯下降,小劑量組無明顯降壓作用.VEGF暘性錶達主要分佈于梗死竈週圍區血管內皮細胞,其錶達隨時間推移進一步上調,再灌註72 h達峰值.Western印跡分析與免疫組化染色結果一緻.結論 坎地沙坦可能通過上調缺血區VEGF錶達縮小腦梗死體積,改善神經功能評分.
목적 탐토감지사탄예처리대뇌결혈대서적혈관보호작용.방법 48지웅성SpragurDawley대서,수궤분위가수술조、결혈재관주조이급감지사탄소제량조[0.1 mg/(kg·d)]화대제량조[1 mg/(kg·d)],매조12지;각조우수궤분위결혈2 h후재관주24 h화재관주72 h아조(매조6지).약물관위4주후,채용선전법제비대뇌중동맥폐새모형,술전측량혈압,분별재재관주24 h화72 h후진행신경공능평분,연후단두취뇌,채용2,3,5-록화삼분기사담서염색측정뇌경사체적,통과면역조화염색화Western인적분석검측결혈구뇌조직혈관내피생장인자(vascular endothelial growth factor,VEGF)단백표체.결과 감지사탄소제량조화대제량조재관주24 h화72 h신경공능평분균현저우우결혈재관주조(P분별위0.008화0.001),뇌경사체적현저축소(P분별위0.010화0.000).감지사탄대제량조재간예후제2주혈압명현하강,소제량조무명현강압작용.VEGF양성표체주요분포우경사조주위구혈관내피세포,기표체수시간추이진일보상조,재관주72 h체봉치.Western인적분석여면역조화염색결과일치.결론 감지사탄가능통과상조결혈구VEGF표체축소뇌경사체적,개선신경공능평분.
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.
