The Study Of HIF-1α And VEGF / VEGFR2 Expression Regulates Angiogenesis After Cerebral Ischemia

Objective:To observe the effect of Naotaifang extract on the cerebral is-chemia reperfusion injury in rat brain tissue angiogenesis. hypoxia indu-cible factor-1α(HIF-1α)、vascular endothelial growth factor (VEGF) and receptor-2(VEGFR-2) and so on, to reveal mechanism of Naotaifang in angiogenesis by promoting the treatment of cerebral infarction.Method:SD rats were randomly divided into three groups:group A: underwent sham operation,group B:underwent an operation of ischemic brain injur, group C:Naotaifang. The middle cerebral artery occlusion (MCAO) of group B and C rats were induced. The time points of reperfusion was 1d,3d,5 d and 7 d following MCAO. According to the time of the ischemia-reperfusion (1,3,5and 7d), B group and C group, were divided into 4 subgroups. All of the animals were evaluated in neurological function and examined by histopathological methods. The neurological deficiency, the volume of cerebral infarction, the density of vessels, the levels of HIF-1α、VEGF and VEGFR2 were measured.Results:1、The score of neurological evaluation:the scores of A were 0 from 1d to 7 d, the scores of B and C were higher than that of A group, compared with A group were statistically significant (p<0.05) in 1d, however, the difference between the two groups was not significant (p>0.05); the scores of C were declined obviously, compared with B group were statistically significant(p<0.05),compared with A group were not significant (p>0.05) in 3d; the scores were declined in 5d and 7d, however,the B group was still significantly higher than A group (p<0.05).2、The volume of cerebral infarction:A group was no significant cerebral; B and C was basically the same as the volume of cerebral infarction in 1d (p>0.05); The volume of cerebral infarction of B gruop didn’t change significantly, but C significantly reduced infarct volume 3d to 7d, compared with B at the same time were significant(p<0.05).3、The microvessel density:the density of vessels of B and C group cortex of ischemic hemisphere incresed than group A in 1d, but no statistical significance (p>0.05). The density of vessels of C group increased obviously (p<0.05), B group increased little (p>0.05) in 3 d. The density of C group increased more obviously, had significant different than A group in 5、7d (p<0.01). B group did not increase continually until showed significant different than A group in 7d(p<0.05).4、Brain tissue expression of HIF-1α:C group brain tissue HIF-1αexpressed 1d namely to achieve the peak, obviously is higher than B group and A group(p<0.01), later would drop gradually; B group HIF-1αexpression had increased, but the difference was not statistically significant in 1d (p>0.05), achieved the peak to 3d, was higher than A group obviously(p<0.05), later would drop gradually.5、Brain tissue expression of VEGF:after ischemia-reperfusion, 1d to 5d, C group brain tissue VEGF expressed obviously increases, obviously was higher than A group (p<0.01),3d achieved the peak; the B group VEGF expression 3d started to have elevates, was higher than A group obviously to 5d (p<0.05),7d dropped; 1d and 3d, C group VEGF expressed obviously was higher than B group(p<0.05).6、Brain tissue expression of VEGFR-2:B group and C group after ischemia-reperfusion, the expression of the cerebral cortex VEGFR-2 started to elevate gradually 1d to 7d, C group achieved the peak 5d, obviously was higher than A group (p<0.01),7d started to drop, but till had the significance difference compared with A group (p<0.01); B group achieved the peak 7d, had the significance difference compared with A group(p<0.01).Conclusion:Naotaifang promots cerebral ischemia-reperfusion injury in rat ischemic brain tissue angiogenesis in order to improve infarct volume and neurological deficits points. The mechanism of promoting angiogenesis had the close relation with regulating HIF-1α、VEGF、VEGFR-2 expression in ischemic border zone.