摘要
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。