三氧化二砷和柔红霉素对急性早幼粒细胞白血病细胞的促凝血活性的影响  

Effect of arsenic trioxide and daunorubicin on procoagulant activity of acute promyelocytic leukemia cells

作　　者：史家岚[1] 李金梅[1] 侯金晓[1] 曹峰林[1] 刘述川[1] 周晋[1] 高春艳[1] 王晶[1] 谭小燕[1] 李甲楠[1] 刘明[1] 刘岩[1] 马瑞爽[1] 杨雪[1] 

机构地区：[1]哈尔滨医科大学附属第一医院血液内科,150001

出　　处：《中华医学杂志》2012年第16期1095-1099,共5页National Medical Journal of China

基　　金：国家自然科学基金（30871227）;黑龙江省科技攻关资助项目（GB08CA.01-02）

摘　　要：目的观察三氧化二砷（ATO）和柔红霉素（DNR）对急性早幼粒细胞白血病（APL）细胞表面磷脂酰丝氨酸（Ps）暴露及促凝血活性的影响。方法提取2007年3月至2009年2月就诊于哈尔滨医科大学附属第一医院的12例初发APL患者的APL细胞，以12份健康志愿者全血中提取的单个核细胞和中性粒细胞作为对照。用1μmol／LATO、DNR分别处理APL细胞24h，通过流式细胞术和共聚焦显微镜检测APL细胞的Ps暴露，通过凝血时间和凝血因子生成实验测定相关的凝血活性。乳黏素作为检测APL细胞PS暴露的探针和凝血抑制剂。结果流式细胞仪和共聚焦显微镜结果显示，与未处理组比较，ATO处理组APL细胞PS暴露减少；而DNR处理组APL细胞PS暴露明显增加。ATO处理组，APL细胞的凝血时间比未处理组长[（220±41）s比（180±25）S，P〈0．05]，凝血因子生成比未处理组少（均P〈0．05）；而DNR处理组，APL细胞的凝血时间比未处理组短[（80-1-20）s比（180±25）s，P〈0．05]，凝血因子生成比未处理组多（均P〈0．05）。加入乳黏素后，DNR处理组APL细胞的促凝活性降低[内源性、外源性凝血因子Xa及凝血酶生成均减少（均P〈0．05）]。结论APL细胞的PS暴露量与其促凝活性呈正相关。ATO通过减少APL细胞表面的PS暴露而减弱其促凝活性，DNR通过增加APL细胞表面PS暴露而增强其促凝血活性。Objective To explore the effect of arsenic trioxide （ATO） and daunornbicin （DNR） on phosphatidylserine （PS） exposure and related procoagulant activity of acute promyelocytic leukemia （APL） cells. Methods Mononuclear cell and neutrophil isolated from whole blood of 12 healthy volunteers were used as control group while APL cells obtained from 12 newly diagnosed APL patients at First Affiliated Hospital, Harbin Medical University from March 2007 to February 2009 were used as experimental group. APL cells were treated with 1 μmol/L ATO and 1 μmol/L DNR for 24 h. PS exposure of APL cells were measured by flow cytometry and confocal microscopy. And the related procoagulant activity was detected by the assays of coagulation time and coagulation factor formation. Laetadherin was used as a probe for PS exposure and anticoagulant on the cells of 12 APL patients. Results ATO induced a decrease of PS exposure on APL cells by flow eytometry and no staining with laetadherin was observed under confoeal microscopy. However, DNR induced the significantly elevated PS exposure and staining green with a rim pattern on membrane of APL cells was obtained. Coagulation time was （ 180 ± 25 ） s and （ 220 ± 41 ） s before and after treatment with ATO, respectively （ P 〈 0. 05 ） . The formation of coagulation factors decreased after treatment with ATO （P 〈 0. 05 ）. While coagulation time was （180 ± 25 ） s and （80 ± 20） s before and after treatment with DNR, respectively （P 〈 0. 05 ） . The formation of coagulation factors increased after treatment with DNR （ all P 〈 0. 05 ）. Laetadherin inhibited the proeoagulant activities of DNR-treated APL cells （ all P 〈 0. 05）. Conclusions Procoagulant activity is positively correlated with theexposed PS of APL cells. ATO and DNR inhibited and enhanced procoagulant activity with decreased and increased PS exposure, respectively.

关 键 词：白血病 早幼粒细胞 急性 砷剂 柔红霉素 磷脂酰丝氨酸类 乳黏素 

分 类 号：R733.7[医药卫生—肿瘤]