Objective: To explore the changes of endostatin (a strong anti-angiogenesis factor) and vascular endothelial growth factor (VEGF) in the brain tissues of rabbits following cerebral ischemia induced by middle cerebral artery occlusion (MCAO).
Methods: Twenty-four New Zealand white rabbits were randomly divided into 5 groups: control (n = 5), sham-operation (n = 4), 2-hour ischemia (n = 5), 24-hour ischemia (n = 5), and 48-hour ischemia (n = 5). The expression of VEGF and endostatin were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. In situ hybridization was used to characterize the expression of mRNA for the endostatin.
Results: Both the protein (at least 50%, P < 0.01) and mRNA (at least 70%, P < 0.05) of endostatin increased significantly in the ischemic brain tissues after MCAO compared with the control group. VEGF increased at least 270% in the brain after cerebral ischemia (P < 0.05).
Conclusion: Cerebral ischemia leads to an up-regulation of endostatin in the brain, which is not associated with the increase of VEGF in the brain. The increase of endostatin may serve as a deleterious mechanism for ischemic injury through blocking angiogenesis.
目的: 内皮抑素(endostatin)是强烈的抗血管再生因子。 本文探讨大脑中动脉闭塞 (middle cerebral artery occlusion, MCAO) 致局灶性脑缺血后脑组织内皮抑素蛋白及mRNA基因表达的变化, 同时检测缺血脑组织血管内皮生长因子(vascular endothelial growth factor, VEGF)的含量。
方法: 24只新西兰白兔随机分为正常对照组(n = 5)、; 假手术组(n = 4)、 缺血2 小时组(n = 5)、 缺血 24 小时组 (n = 5)及缺血48 小时组(n = 5)共5 组。 酶联免疫吸附试验测定VEGF 含量, 免疫组化分析内皮抑素蛋白变化, 原位杂交检测内皮抑素mRNA表达。
结果: 与对照组相比, MCAO局灶性脑缺血后内皮抑素蛋白和mRNA表达均明显增加, 至少分别增加了50%(P < 0.01)和70%(P < 0.05), 同时缺血脑组织VEGF 含量也明显增加, 至少增加了270%。
结论: 缺血导致脑组织内皮抑素表达增加?且内皮抑素的增加与缺血后脑组织VEGF 变化无相关性, 但可能抑制脑缺血后的血管再生, 从而加重脑缺血损伤。