实验性脑出血大鼠血肿周围VEGF、bFGF表达及血管新生的动态变化及重组人促红细胞生成素对其干预作用的研究

The effects of recombinant human erythropoietin on the expression of VEGF,bFGF and angiogenesis in rat brain with intracerebral hemorrhage

目的研究大鼠脑出血后血管内皮细胞生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)表达的动态变化及血管新生情况,以及重组人促红细胞生成素(rhEPO)对其的干预作用,探讨rhEPO对脑出血的可能保护机制。方法采用自体血脑内注入法建立脑出血动物模型。168只雄性SD大鼠随机分为正常组、假手术组、模型组、rhEPO治疗组。免疫组化法检测VEGF、bFGF、CD34的表达变化,用CD34的表达来反映血管新生情况。结果脑出血后3h即有VEGF表达增多,7～14d达高峰;bFGF的表达6h开始增多,72h达高峰;CD34+血管数12h开始增多,14d达高峰。rhEPO治疗组6h～21d时VEGF、bFGF表达比模型组高(P<0.05或P<0.01),且VEGF表达于72h～7d时提前达高峰;12h～21d时CD34+血管数高于模型组(P<0.01),且于7d时提前达高峰。结论rhEPO能上调脑出血后VEGF、bFGF的表达,促进脑出血后血肿周围新生血管生成。

Objective To study the protein expression changes of vascular endothelial growth factor（VEGF）,basic fibroblast growth factor（bFGF）and angiogenesis in rat brain with intracerebral hemorrhage（ICH）and the effects of recombinant human erythropoietin（rhEPO）on them,to reveal the mechanism of neuroprotection by rhEPO.Methods The model of ICH was established in rats by intracerebral injection of autogenous blood.168 male Spranue-Dawley rats were randomly divided into normal control group,sham-operated group,ICH model group and rhEPO-treated group.The protein expression of VEGF,bFGF and CD34 were detected by immunohistochemistry straining.Microvascular production was measured by expression changes of CD34.Results After intracerebral hemorrhage,the expression of VEGF increaesed at 3h and peaked at 7~14d;the expression of bFGF increased at 6h,and peaked at 72h;the expressions of CD34＋ microvascular was increaesed at 12h and peaked at 14d.Compared to the ICH model group,the expressions of VEGF and bFGF in rhEPO-treated group increased at 6h^21d（P0.05 or P0.01）,and the expression of VEGF early peaked at 72h^7d.The expressions of CD34＋ microvascular in rhEPO-treated group were increased at 12h^21d（P0.01）and early peaked at 7d.Conclusion rhEPO could up-regulate the expressions of VEGF and bFGF and enhance angiogenesis.