重组粒细胞集落刺激因子对大鼠急性缺血性脑梗死后损伤修复的研究

Effects of recombinant human granulocyte colony-stimulating factor on rehabilitation following focal cerebral infarction in rats

目的观察人重组粒细胞集落刺激因子(rhG-CSF)对大鼠急性局灶性脑梗死轴突、血管再生的影响。方法健康雄性Wistar大鼠建立局灶性脑缺血模型,随机分为脑缺血组及相应时间点的假手术组、药物组。免疫组织化学法检测脑内血管内皮细胞生长因子(VEGF)变化及反转录-聚合酶链反应(RT-PCR)法检测神经生长相关蛋白(GAP)-43表达。结果①缺血组及药物组1～10d GAP-43均呈增高趋势,2组各时间表达量有区别;②缺血组VEGF表达1～10d内缓慢增高;药物组上调VEGF表达,1～4d迅速增高,4d时达到高峰,4～10d有降低趋势,10d与假手术组相比仍有差别。结论G-CSF可促进轴突再生、血管增殖,延长缺血治疗窗,发挥脑保护作用。

Objective To investigate whether recombinant human granulocyte colony-stimulating factor （rhG- CSF） may benefit regeneration of neural axons and blood vessels after the focal cerebral infarction in rats. Methods Model of focal cerebral infarction was established in healthy male Wistar rats. The rats were randomly assigned to the ischemia group, drug group and the sham operated group, then the transient focal ischemia injury was induced. Immunohistological staining was used to detect vascular endothelial growth factor （VEGF） expression and reverse transcription polymerase chain reaction （RT-PCR） was used to verify growth-associated protein 43 （GAP-43） expression. Results （1）During days I to 10, GAP-43 expression appeared to have an ascending trend in both ischemia group and drug group, but was different in level of expression between these two groups at every time point. （2）The expression of VEGF increased slowly during days 1 to 10 in the ischemia group （P〈0.05）, whereas in the drug group, VEGF showed a rapid up-regulated expression during days 1 to 4, peaked on day 4, then tended to decline during days 4 to 10. Difference in VEGF expression was significant between the drug group and sham operated group even on day 10. Conclusion G-CSF was shown to promote regeneration of neural axons and proliferation of blood vessels, which may extend the time window for treatment of thrombolysis and achieve significant neuro-protective effects.