雷公藤红素阻断全反式维甲酸导致的白血病细胞与内皮细胞黏附  

Tripterine inhibits all-trans retinoic acid-caused adhesion between leukemia cells and endothelial cells

作　　者：徐莉敏[1] 张登海[1] 杨春欣[2] 刘旭辉 Geroges UZAN 秦万章[4] 

机构地区：[1]上海市浦东新区公利医院中法联合实验室,上海200135 [2]复旦大学上海医学院中山医院药剂科,上海200032 [3]法国国家医学与健康研究院602研究单位,法国巴黎94807 [4]复旦大学上海医学院中山医院皮肤科,上海200032

出　　处：《中西医结合学报》2007年第3期282-286,共5页Journal of Chinese Integrative Medicine

基　　金：上海浦东新区卫生科技项目资助(No.PW2006A-17)

摘　　要：目的:全反式维甲酸(all-trans retinoic acid,ATRA)治疗急性早幼粒细胞白血病,引起白血病细胞与内皮细胞之间黏附增加,是发生维甲酸综合征的重要原因。本文观察雷公藤红素对这种黏附增加的影响。方法:用流式细胞术检测雷公藤红素对急性早幼粒细胞白血病细胞系NB4和人脐静脉内皮细胞(humanumbilical vascular endothelial cell,HUVEC)在ATRA刺激下表达黏附分子的影响。用细胞黏附功能实验,检测雷公藤红素对ATRA导致的上述两种细胞之间黏附增加的影响。结果:ATRA能引起NB4细胞表面细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)表达增加,但可被雷公藤红素明显抑制(P<0.01)。NB4细胞上清液能刺激HUVEC表达ICAM-1(P<0.05);而被ATRA处理过的NB4细胞上清液能明显刺激HUVEC表达选择素E(E-selectin)、血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)和ICAM-1等黏附分子(P<0.01),雷公藤红素对其抑制率分别达25.3%、42.4%和61.0%。ATRA导致上述两种细胞之间黏附增加,雷公藤红素对其完全抑制。结论:雷公藤红素能抑制ATRA导致的白血病细胞与内皮细胞黏附,有可能用于维甲酸综合征的治疗。Objective： Increasing of adhesion between leukemia cells and endothelial cells during all-trans retinoic acid （ATRA） treatment plays an important role in retinoic acid syndrome. This work observed the effects of tripterine on this ATRA-caused increasing in adhesion. Methods： The effects of tripterine on ATRA-induced expressions of adhesive molecules in acute promyelocytic leukemia cell line NB4 and human umbilical vascular endothelial cells （HUVEC） were detected by flow cytometry. The effects of tripterine on adhesion between ATRA-treated NB4 and HUVEC were determined by adhesive assays. Results： ATRA caused remarkable elevation of intercellular adhesion molecule-1 （ICAM-1） in NB4 cells, which could be significantly reduced by tripterine （ P 〈 0. 01）. The expressions of E-selectin, vascular cell adhesion molecule-1 （VCAM-1） and ICAM-1 in HUVEC were elevated by conditioned medium from ATRA- induced NB4 （ATRA-NB4-CM） （ P〈0.01）, and inhibited by tripterine with inhibition rates being 25.3%, 42.4% and 61. 0% respectively. ATRA increased the adhesion between NB4 and HUVEC, which was reversed completely by tripterine. Conclusion： Tripterine can inhibit ATRA-caused adhesion between leukemia cells and endothelial cells, and it might be a potential agent for treating retinoic acid syndrome.

关 键 词：雷公藤红素 维甲酸 细胞间黏附分子-1 血管细胞黏附分子-1 选择素E 

分 类 号：R733.7[医药卫生—肿瘤]