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首页> 外文期刊>Journal of stroke and cerebrovascular diseases: The official journal of National Stroke Association >Targeted Delivery of Extracellular Matrix Protected against Neurologic Defects after Focal Ischemia Reperfusion in Rats
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Targeted Delivery of Extracellular Matrix Protected against Neurologic Defects after Focal Ischemia Reperfusion in Rats

机译:大鼠局部缺血再灌注后针对神经功能缺损保护的细胞外基质的靶向递送。

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`Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and characterized by defective angiogenesis. The functional sequences (RGDs, GRGDSPASSPISC) derived from fibronectin have been confirmed to augment angiogenesis in vivo and in vitro. However, delivery of peptides into the brain parenchyma has been hampered by the presence of the blood-brain barrier (BBB). We fused RGDs with penetratin (Antp) derived from Drosophila antennapedia homeodomain protein to improve the penetration of peptides through BBB into ischemic hemisphere. We found Antp-RGDs successfully not only penetrate the SH-SY5Y cells but also penetrated through BBB into ischemic hemisphere by intraperitoneal injection. In addition, application of Antp-RGDs to the focal cerebral ischemic reperfusion injury in rats resulted in the reduction of cerebral ischemic volume and the improvement of neurologic score according to the 21-point score. We further demonstrated that activation of phosphorylation-extracellular-signal related kinase 1/2 (p-ERK1/2) and upregulation of gene VEGF resulted from post-treatment with Antp-RGDs 2 hours after reperfusion onset might at least partly contribute to the benefic changes after focal cerebral ischemic reperfusion injury in rats. Our data suggested that Antp-RGDs may serve as an attractive therapeutic intervention for treating ischemic stroke.
机译:缺血性中风是全世界发病率和死亡率的主要原因之一,其特征是血管生成缺陷。已证实衍生自纤连蛋白的功能序列(RGD,GRGDSPASSPISC)可增强体内和体外的血管生成。然而,由于血脑屏障(BBB)的存在,阻碍了肽向脑实质的递送。我们将RGD与果蝇触角同源结构域蛋白的Penetratin(Antp)融合在一起,以提高肽通过BBB进入缺血性半球的渗透性。我们发现,Antp-RGDs不仅可以成功地穿透SH-SY5Y细胞,而且还可以通过腹膜内注射通过BBB进入缺血性半球。此外,将Antp-RGDs应用于大鼠局灶性脑缺血再灌注损伤后,脑缺血量减少,神经系统评分提高了21分。我们进一步证明了由再灌注发作后2小时用Antp-RGDs后处理引起的磷酸化-细胞外信号相关激酶1/2(p-ERK1 / 2)的激活和基因VEGF的上调可能至少部分有助于受益大鼠局灶性脑缺血再灌注损伤后的变化我们的数据表明,Antp-RGDs可以作为治疗缺血性中风的诱人治疗手段。

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