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

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。

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

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.