三氧化二砷联合柔红霉素对早幼粒白血病细胞凋亡和凝血作用的影响  

Effect of ATO combined with DNR on the apoptosis and procoagulant activity of promyelocytic leukemia cells

作　　者：杨昆鹏[1] 侯金晓[1] 刘亚波[1] 祁森[1] 苏雁华[1] 

机构地区：[1]哈尔滨医科大学附属第一医院血液内科,哈尔滨150001

出　　处：《临床血液学杂志》2014年第3期393-396,共4页Journal of Clinical Hematology

基　　金：黑龙江省自然科学基金(No:D200861);黑龙江省政府博士后启动基金(No:LRB2010-301);高等学校博士学科点专项科研基金资助(No:20112307110012)

摘　　要：目的：探讨三氧化二砷（ATO）与柔红霉素（DNR）联合应用对原代急性早幼粒白血病（APL）细胞及早幼粒白血病细胞株NB4凋亡和凝血的影响。方法：采用ATO、DNR、ATO＋DNR处理APL和NB4细胞等3组体外液体培养法,空白对照组不加任何药。采用流式细胞仪和共聚焦显微镜观察各组细胞凋亡,用复钙时间检测各组APL和NB4细胞的促凝活性,采用ELISA法测定各组NB4细胞组织因子（TF）、血栓调节蛋白和膜联蛋白Ⅱ（annexinⅡ）的表达。结果：ATO与DNR联合用药处理APL和NB4细胞后,其凋亡率较空白对照组提高4-8倍,促凝血活性明显降低,NB4细胞的TF和annexinⅡ表达均显著减少（均P〈0.05）。结论：ATO与DNR联合用药能有效促进APL和NB4细胞凋亡,且不加重凝血紊乱,其可能是通过降低TF和annexinⅡ的表达抑制凝血和纤溶亢进等改善APL的凝血功能,此联合用药对于原发高白细胞型APL的治疗可能是一种安全、有效的方法。Objective：To explore the effect of arsenic trioxide（ATO）combined with daunorubicin（DNR）on the apoptosis and procoagulant activity of APL and NB4cells.Method：After being cultivated in vitro,the APL and NB4cells were treated with ATO,DNR and ATO plus DNR.Then the procoagulant activity of these cells was assessed by determining recalcification time and the effect of these drugs on apoptosis of APL and NB4cells was demonstrated by flow cytometry and confocal microscopy.After that,we tested the expression of tissue factor（TF）,thrombomodulin and annexinⅡin NB4cells with the ELISA method.Result：ATO combined with DNR could remarkably reduce the procoagulant activity of APL and NB4cells and increase the apoptosis rate of APL and NB4 cells（at least 4to 8fold compared to the control group,P〈0.05）.After the treatment of ATO and DNR,the expression of TF and annexinⅡin NB4cells decreased（compared with the control group separately,P〈0.05）.Conclusion：ATO combined with DNR could effectively enhance the apoptosis rate of APL cells without aggravation of coagulation disturbance.This combined therapy could ameliorate the coalulation disturbance in APL,which may be through the inhibition of blood coagulation and hyperfibrinolysis by the reduction of TF and annexinⅡ.ATO combined with DNR may be a safe and effective therapy for remission induction in APL with initial leukocytosis.

关 键 词：急性早幼粒白血病 三氧化二砷 柔红霉素 促凝活性 凋亡 

分 类 号：R733.71[医药卫生—肿瘤]