Role of vascular endothelial growth factor in neuronal DNA damage and repair in rat brain following a transient cerebral ischemia
Role of vascular endothelial growth factor in neuronal DNA damage and repair in rat brain following a transient cerebral ischemia
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DOI：
10.1002/jnr.10380
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发表时间：
2002-10
影响因子：
4.2
通讯作者：
Zeng-Jin Yang;W. Bao;M. Qiu;Ling-mei Zhang;Shilong Lu;Ya-Lin Huang;F. Sun
中科院分区：
文献类型：
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作者：
Zeng-Jin Yang;W. Bao;M. Qiu;Ling-mei Zhang;Shilong Lu;Ya-Lin Huang;F. Sun
采用反义敲除技术和共焦激光扫描显微分析来阐明血管内皮生长因子 (VEGF) 的诱导及其对大脑中动脉短暂闭塞后大鼠大脑 DNA 损伤和修复的影响。免疫组化和原位杂交显示，缺血脑缺血核心区和半影区VEGF及其mRNA表达增强。蛋白质印迹分析进一步表明，VEGF 诱导在这些区域中呈时间依赖性变化。双染色分析表明 VEGF 阳性染色存在于神经元中，但不存在于神经胶质细胞中，并且它与 DNA 修复因子切除修复交叉互补组 6 (ERCC6) mRNA 共定位。 VEGF 反义寡脱氧核苷酸输注减少了 VEGF 诱导，导致缺血引起的脑梗塞体积扩大。此外，它还增加了 DNA 受损细胞的数量，并减少了缺血大脑中 ERCC6 mRNA 的诱导。这些结果表明，缺血神经元中内源性 VEGF 的诱导发挥了神经保护作用，可能与 ERCC6 mRNA 的表达有关。 © 2002 Wiley-Liss, Inc.
The antisense knockdown technique and confocal laser scanning microscopic analysis were used to elucidate vascular endothelial growth factor (VEGF) induction and its effect on DNA damage and repair in rat brain following a transient middle cerebral artery occlusion. Immunohistochemical study and in situ hybridization showed that the expression of VEGF and its mRNA was enhanced in the ischemic core and penumbra of ischemic brain. Western blot analysis further illustrated that VEGF induction was time‐dependently changed in these areas. Double‐staining analysis indicated that VEGF‐positive staining existed in the neuron, but not in the glia, and it colocalized with excision repair cross‐complementing group 6 (ERCC6) mRNA, a DNA repair factor. VEGF antisense oligodeoxynucleotide infusion reduced VEGF induction and resulted in an enlargement of infarct volume of the brain caused by ischemia. Moreover, it also increased the number of DNA damaged cells and lessened the induction of ERCC6 mRNA in ischemic brains. These results suggest that the induction of endogenous VEGF in ischemic neurons plays a neuroprotective role probably associated with the expression of ERCC6 mRNA. © 2002 Wiley‐Liss, Inc.