目的 觀察普納替尼(Ponatinib)對(duì)人血管內(nèi)皮細(xì)胞的增殖、遷移、血管形成及NO合成釋放的影響, 從細(xì)胞水平評(píng)價(jià)Ponatinib血栓不良反應(yīng)形成機(jī)制。方法 采用CCK-8法、體外劃痕法、Matrigel基底膜成管法及NO檢測試劑盒分別考察Ponatinib對(duì)人臍靜脈內(nèi)皮細(xì)胞(HUVECs)的細(xì)胞毒作用、遷移能力、血管形成能力及細(xì)胞NO釋放水平的影響。結(jié)果 研究表明Ponatinib對(duì)HUVECs細(xì)胞半數(shù)抑制濃度(IC₅₀)為(0.69±0.05)μmol/L。非毒性劑量的Ponatinib能夠不同程度抑制HUVECs細(xì)胞的遷移、血管形成及NO的釋放(P<0.05)。結(jié)論 Ponatinib通過影響人血管內(nèi)皮細(xì)胞增殖、遷移、血管形成等正常功能而造成血管內(nèi)皮損傷, 可能為其誘發(fā)血栓的原因之一。

Objective To investigate the effect of Ponatinib on human vascular endothelial cell proliferation, migration, angiogenesis and the synthesis and release of NO and to evaluate the mechanisms of thrombotic adverse reaction of Ponatinib in vitro. Methods CCK-8 assay, wound healing test, tube formation assay, and NO detection Kit were used to investigate the cytotoxicity, migration, angiogenesis, and NO release of Ponatinib on human umbilical vein endothelial cells (HUVECs). Results It was found that the IC₅₀ value of Ponatinib on HUVECs was (0.69 ± 0.05) μmol/L. Non-toxic concentration of Ponatinib was able to inhibit the proliferation, migration, angiogenesis, and NO release (P < 0.05). Conclusion Ponatinib may injure the vascular endothelial cells by inhibiting the proliferation, migration, angiogenesis, and other functions of human vascular endothelial cells, which might be one of the main mechanisms of thrombotic adverse reaction, so as to provide the references for future research on the thrombosis mechanisms of Ponatinib.