柔红霉素对急性早幼粒细胞白血病细胞释放的微粒的数量及促凝活性的影响  

Effect of Daunorubicin on Release and Procoagulant Activity of Microparticles Derived from Acute Promyelocytic Leukemia Cells

作　　者：李海涛[1] 赵淑艳[2] 刘志宇[1] 侯金晓[1] 张迎媚[1] 杨东光[1] 王萍[3] LI Hai-Tao;ZHAO Shu-Yan;LIU Zhi-Yu;HOU Jin-Xiao;ZHANG Ying-Mei;YANG Dong-Guang;WANG Ping(Centerfor Hematology and Oncology,The First Affiliated Hospital,Harbin Medical University,Harbin,150001,Heilongjiang Province,China;Department of Oncology,The First Affiliated Hospital,Heilongjiang University of Traditional Chinese Medicine,Harbin 150000,Heilongjiang Province,China;Department of Newborn,The First Affiliated Hospital,Harbin Medical University,Harbin 150001,Heilongjiang Province,China)

机构地区：[1]哈尔滨医科大学附属第一医院血液肿瘤中心,黑龙江哈尔滨150001 [2]黑龙江中医药大学附属第一医院肿瘤科,黑龙江哈尔滨150000 [3]哈尔滨医科大学附属第一医院新生儿科,黑龙江哈尔滨150001

出　　处：《中国实验血液学杂志》2018年第4期972-977,共6页Journal of Experimental Hematology

基　　金：黑龙江省卫生厅科研课题(2007-211)

摘　　要：目的:研究柔红霉素(DNR)对急性早幼粒细胞白血病(APL)细胞释放的微粒(MP)的数量及其促凝活性的影响。方法:提取5例初发APL患者骨髓APL细胞;提取5例缺铁性贫血患者骨髓单个核细胞作为对照。用不同浓度的DNR(0.1,0.5,1.0和2.0μmol/L)处理APL细胞24 h,收集细胞培养液提取MP。透射电子显微镜观察提取的微粒的形态学特点,并对其进行定性分析。流式细胞术检测MP数量;应用一步复钙时间法测定MP的促凝血活性。结果:提取的微粒呈现出圆形或椭圆形的中空囊性结构,其直径为100 nm左右,符合微粒的形态学特点。与正常骨髓单个核细胞释放的MP数量相比,骨髓APL细胞释放的MP数量增加(P<0.05)。DNR促进APL细胞释放MP,且这一作用呈剂量依赖性(r=0.73,P<0.01)。与对照组骨髓单个核细胞释放的MP相比较,APL细胞释放的MP促凝活性显著增高(P<0.05)。DNR处理可显著增强MP的促凝活性,且这一作用呈剂量依赖性(r=-0.78,P<0.01)。结论:DNR可促进APL细胞释放MP,并且增强这些MP的促凝活性。Objective： To investigate the effect of daunorubicin on the number and procoagulant activity of microparticles derived from acute promyelocytic leukemia（ APL） cells. Methods： APL cells were isolated from bone marrow of 5 newly diagnosed APL patients,the bone marrow mononuclear cells were collected from 5 patients with iron deficiency anemia as control. APL cells were treated with different concentration of daunorubicin（ 0. 1,0. 5,1. 0 and 2. 0 μmol/L） for 24 h. Microparticles were extracted from the cell culture medium for qualitative analysis of the extracted microparticles. The morphologic features of the microparticles were observed by transmission electron microscopy. The number of microparticles was detected by flow cytometry. The procoagulant activity of microparticles was measured by recalcification time assays. Results： Under a transmission electron microscope,the extracted microparticles took a round or oval morphology with a transparent center,and their diameters were around 100 nm,consistent with the morphological characteristics of microparticles. Compared with bone marrow mononuclear cells-derived microparticles,the counts of the bone marrow APL cells-derived microparticles significantly increased（ P〈0. 05）. Daunorubicin increased the shedding of microparticles in a dose-dependent manner（ r = 0. 73,P〈0. 01）.Compared with normal bone marrow mononuclear cells-derived microparticles,bone marrow APL cells-derived microparticles showed higher procoagulant activity（ P〈0. 05）. Daunorubicin treatment enhanced the procoagulant activity of APL cells-derived microparticles which paralleled the increasing drug concentrations（ r =-0. 78,P〈0. 01）. Conclusion： Daunorubicin can promote the release of APL cells-derived microparticles and enhance their related procoagulant activity.

关 键 词：急性早幼粒细胞白血病 微粒 柔红霉素 凝血功能紊乱 

分 类 号：R733.71[医药卫生—肿瘤]