氨甲环酸对体外人脐静脉内皮细胞损伤的保护作用

Tranexamic Acid Ameliorates the Injury of Human Umbilical Vein Endothelial Cells in Vitro

目的研究氨甲环酸(tranexamic acid,TXA)对H_2O_2诱导人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)损伤的保护作用及给药时机选择。方法体外培养HUVECs,加入100μmol/L的H_2O_2作用12h,在H_2O_2作用开始后30min和60min以及H_2O_2作用结束前1h和2h这4个时间点加入TXA (150μmol/L); Hoechst 33258染色法观察HUVECs形态; Western blot法检测细胞内细胞间黏附分子(intercellular cell adhesion molecule,ICAM)的表达;酶联免疫吸附双抗体夹心法(ELISA)检测细胞上清液多配体聚糖、t PA和PAI-1含量。结果 HUVECs经H_2O_2作用后,可显著诱导细胞凋亡,上调ICAM、多配体聚糖和t PA的表达,同时抑制PAI-1的表达; TXA在H_2O_2作用60min内给药可抑制H_2O_2对HUVECs的凋亡诱导作用,同时下调ICAM、多配体聚糖和t PA的表达,并上调PAI-1的表达,TXA在60min后给药无上述保护作用。结论早期TXA给药对H_2O_2诱导HUVECs损伤有明显抗纤维蛋白溶解和保护作用,从而表明临床应用TXA需早期给药。

Objective To investigate the protective effect of tranexamie acid (TXA)on human umbilical vein endothelial eells (HUVECs)following H2O2 injury.Methods In vitro HUVECs were exposed to H2O2 to stimulate post -shock reperfusion.TXA was added during H2O2 incubation (30 minutes and 60 minutes)and at 1 hour and 2 hours before the termination of H2O2 exposure.The cellular morphology was observed using a fluorescence mieroseope after Hoechst 33258 staining.Endothelial eell injury was indexed by ICAM expression,syndeean release (marker for glycoealyx injury),tissue type plasminogen activator (tPA)and plasminogen activator inhibitor-1(PAI -1).Results Endothelial activation and injury as indexed by apoptosis and ICAM expression were increased by H2O2 incubation.Biomarkers of endothelial coagulation profile (tPA/PAI -1)demonstrated a profibrinolytie profile (increased tPA and tPA/PAI -1 ratio)after H2O2 treatment.TXA administration within 60minutes of H2O2 treatment abolished the adverse effects of HUVECs induced by H2O2.TXA administration after 60 minutes was not proteetive effect on HUVECs.Conclusion Antifibrinolytie and other protective effects of TXA administration on endothelial injury are time -dependent.This study supports the concept that the clinical effieaey of TXA administration requires "early administration".