Angiogenesis therapy against cerebral ischemic disease

缺氧诱导因子1（HIF-1）是调节哺乳动物细胞对缺氧适应性反应的转录因子。它由一个调控亚基HIF-1α和组成性表达亚基HIF-1β组成，HIF-1α在hypmic条件下积累。我们研究了HIF-1α裸dna在脑缺血模型中诱导的血管生成。我们利用大鼠脑肌合症模型，在脑表面或颞肌上接种HIF-1α裸DNA。我们分析了HIF-1α诱导的血管生成因子和侧支循环。HIF-1α DNA处理的组织学切片显示HIF-1α和VEGF在侧支循环中的表达增加，与对照DNA相比，HIF-1α转录因子能够显著促进血管生成的发展。香叶酰香叶酰丙酮（GGA）被认为是一种抗核剂，最近被用作热休克蛋白（HSP）诱导剂。本研究探讨了GGA对永久性左大脑中动脉闭塞所致大鼠脑梗死的神经保护作用。在缺血前48小时口服GGA单次（800 mg/kg）预处理可显著减少脑梗死体积。在缺血或不缺血的gga处理动物的新皮层中发现HSP70免疫反应性显著增加。单剂量口服GGA预处理为探讨脑缺血神经元损伤的神经保护机制提供了重要工具。

Hyoxia-inducible factor 1(HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1α, which accumulates under hypmic conditions, and constitutively expressed subunit, HIF-1β. We investigated HIF-1α naked DNA-induced angiogenesis in a cerebral ischemic model in vivo. We utilized a rat encephalo-myo-synangiosis model and inoculated HIF-1α naked DNA on the brain surface or temporal muscle. We analyzed HIF-1α induced angiogenic factors and collateral circulation. A histological section treated with HIF-1α DNA showed an increased expression of HIF-1α and VEGF with collateral circulation, in comparison with control DNA HIF-1α transcription factor is able to promote significant angiogenesis development.Geranylgeranylacetone (GGA) is known as an antinuclear agent and more recently as a heat shock protein (HSP) inducer. This study evaluated the neuroprotective effect of GGA against cerebral infarction induced by permanent left middle cerebral artery (MCA) occlusion in rats. GGA was given orally in various regimens prior to MCA ocdusion Pretreatment with a single oral GGAdose (800 mg/kg) 48 hours before ischemia significantly attenuated cerebral infarction volume. A significant increase in HSP70 immunoreactivity was found in the neocortex in GGA-treated animals with or without ischemia. Pretreatment with a single oral dose of GGA provides an important tool for exploring the mechanisms of neuroprotection against cerebral ischemic neuronal damage.