神经纤毛蛋白-1调控血管内皮细胞增殖迁移的功能作用和潜在机制研究

目的 研究神经纤毛蛋白-1（Neuropilin-1，NRP1）在血管内皮细胞（Vascular Endothelial Cells, VECs）增殖迁移中的功能作用及潜在机制。 方法 通过基因干扰腺病毒靶向抑制NRP1的表达，行CCK-8实验研究NRP1下调后对VECs增殖活力的影响，采用流式细胞术研究NRP1下调后对VECs凋亡的影响，行Transwell实验研究NRP1下调后对VECs迁移能力的影响；此外，通过Western Blot检测NRP1下调后对其下游信号通路蛋白表达的影响。 结果 CCK-8实验结果显示下调NRP1表达可抑制大鼠VECs的增殖活力，流式细胞凋亡实验结果显示下调NRP1表达可促进大鼠VECs的凋亡，Transwell实验结果显示下调NRP1表达可抑制大鼠VECs的迁移能力。通过Western Blot检测发现NRP1下调后，下游信号通路蛋白Akt、ERK1/2及NF-kB的磷酸化水平均显著降低。 结论 NRP1可能通过激活PI3K/Akt、MAPK/ERK及NF-kB信号通路促进VECs的增殖与迁移，在静脉桥再内皮化进程中发挥潜在的促进作用。

The functional role and potential mechanisms of neuropilin-1 in regulating the proliferation and migration of vascular endothelial cells

Objective To explore the functional role of neuropilin-1 in the progression of proliferation and migration of vascular endothelial cells. Methods NRP1 was down-regulated using adenovirus mediated shRNA in rat VECs, and we investigated the effect of NRP1 inhibition on VEGF-induced VECs activation. CCK-8 assay was used to analyse cell proliferation, and flow-cytometric analysis was performed for the detection of apoptosis, and transwell assay was applied to analyse cell migration. Western Blot assay was used to examine the effect of NRP1 inhibition on the expression of signalling pathway protein in rat VECs. Results The proliferation and migration of rat VECs could be inhibited after down-regulation of NRP1 using adenovirus mediated shRNA, and the increase of apoptosis was also observed. Besides, inhibition of NRP1 significantly reduced Akt, ERK1/2 and NF-kB phosphorylation in rat VECs. Conclusion NRP1 has a potential role in promoting the proliferation and migration of VECs possibly via activating Akt, ERK1/2 and NF-kB phosphorylation.