目的： 查明阿帕替尼通过血管内皮生长因子受体（vascular endothelial growth factor receptor,VEGFR） 通路促进内皮细胞的自噬和凋亡的作用及其潜在机制。方法： 将人脐静脉内皮细胞（human umbilical vein endothelial cells,HUVEC）与不同浓度的阿帕替尼孵育48h,检测细胞活力、细胞凋亡和自噬水平;活性氧 簇（reactive oxygen species,ROS）试剂盒检测ROS的生成水平;蛋白质免疫印迹法检测磷酸化 VEGFR-2、 磷酸化哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）、mTOR、磷酸化 Akt、Akt 的表达水平。结果： 阿帕替尼促进细胞自噬和凋亡,并降低细胞活力,在浓度为 40 mol·L-1时达到最优（凋亡率从1.31%±0.08%增加到22.43%±2.90%,细胞活力从 100%±8.20% 降低到 11.42%±1.08%）;同时,阿帕替尼显著降低磷酸化的VEGFR-2,磷酸化的Akt和磷酸化的mTOR 的表达。同时,阿帕替尼显著降低了磷酸化VEGFR-2、磷酸化Akt和磷酸化mTOR的表达。结论： 阿帕替尼通过VEGFR通路促进内皮细胞的自噬和凋亡。
Objective： To investigate the role of apatinib in promoting autophagy and apoptosis of endothelial cells through the vascular endothelial growth factor receptor（VEGFR）pathway and its potential mechanism. Methods： Human umbilical vein endothelial Cells（HUVEC）was incubate with different concentrations of apatinib for 48 h to detect cell viability,apoptosis and autophagy levels;the level of reactive oxygen species （ROS）generation was detected by the ROS detection kit ;the expression levels of phosphorylated VEGFR-2,phosphorylated mammalian target of rapamycin（mTOR）,mTOR,phosphorylated Akt,and Akt were detected by Western blot. Results： Apatinib promoted cell autophagy and apoptosis,and reduces cell viability. The optimal concentration of apatinib was 40mol·L-1（increasing the apoptotic rate from 1.31%±0.08% to 22.43%±2.90%, and cell viability from 100.03%±8.20% down to 11.42%±1.08 %）;at the same time,apatinib significantly reduced the expression of phosphorylated VEGFR-2,phosphorylated Akt and phosphorylated mTOR. Conclusion： Apatinib promotes autophagy and apoptosis of endothelial cells through VEGFR pathway.
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