血管内皮生长因子对发育期癫痫持续状态诱导的远期神经行为学及海马凋亡的影响

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目的:研究血管内皮生长因子(VEGF)对发育期大鼠癫痫持续状态(SE)后神经行为学和海马凋亡蛋白Bax、Bcl-2表达的影响,探讨外源性VEGF的神经保护作用。方法96只生后14 d的SD大鼠随机分为空白对照组、SE组及药物干预组。经立体定向仪向左侧脑室注射VEGF干预,次日再腹腔注射海人酸诱导SE,其中急性期亚组(生后16 d)及远期亚组(生后59 d)均在生后16 d行神经发育学检查及59 d行Morris水迷宫实验,然后分别在生后17 d、65 d取脑组织海马行免疫组化检测海马区Bax、Bcl-2的表达。结果 VEGF组与SE组相比不仅可改善发育期大鼠远期神经行为损害,而且可诱导Bcl-2蛋白及抑制Bax蛋白的表达,VEGF组中,以0.04μg VEGF组Bax蛋白表达的阳性细胞平均光密度值(AOD)最低(急性期0.016±0.004;远期0.028±0.011)(P<0.05),Bcl-2蛋白表达的阳性细胞AOD最高(急性期0.960±0.240;远期0.210±0.025)(P<0.05)。结论 VEGF对发育期SE的惊厥性损伤具有神经保护作用,而以0.04μg VEGF组对脑保护作用最明显。“,”Objective To study the effect of vascular endothelial growth factor (VEGF) on the neuroethology and the expression of apoptosis proteins Bax, Bcl-2 in hippocampus of pubertal status epilepticus rats. To explore the exogenous recombinant vascular endothelial growth factor 165 (rhVEGF-165) neural protection.Methods Ninety-six fourteen days old healthy SD rats were randomly divided into blank control group, SE group, drug intervention group. Stereotactic apparatus was used to inject VEGF to the left ventricle. SE was induced by KA the next day. The acute phase group (postnatal 16 d) and long-term group (postnatal 59 d) were taken neural development studies at postnatal 16 d and Morris water maze experiments at postnatal 59 d and then Hematoxylin-eosin (HE) staining at postnatal 17 d and immunohistochemical to detect the expression of Bax and Bcl-2 of hippocampal cells at postnatal 65 d.ResultsExogenous VEGF pretreatment can not only improve pyramidal cells morphological changes caused by status epilepticus but also induce the expression of protein Bcl-2 and inhibit the expression of protein Bax. The expression of average optical density value (AOD) of protein Bax in positive cells was the lowest (acute group 0.016±0.004; long-term group 0.028±0.011) (P<0.05) and the expression of AOD of protein Bcl-2 in positive cells was highest (acute group 0.960±0.240; long-term group 0.210±0.025) (P<0.05) in group VEGF 0.04μg. In addition it can also improve forward neural behavior damage in pubertal rats. Conclusion VEGF pretreatment can have the neuroprotection in the development status epilepticus rats, while group VEGF 0.04μg have the most obvious effect on brain protection.
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