Effect of pretreatment with candesartan on the expression of vascular endothelial growth factor after cerebral ischemia-reperfusion in rats / 国际脑血管病杂志

ABSTRACT

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.