亚砷酸诱导分化的急性早幼粒细胞白血病细胞浸润人肺组织的体外模拟试验研究

Simulated experiment in vitro of APL specialized by arsenic trioxide acid infiltrating into the human lung

目的探讨维甲酸和亚砷酸诱导治疗急性早幼粒细胞白血病(APL)时引起的维甲酸综合征(RAS)发生的分子机制及治疗方法。方法2006年1月至2007年2月对哈尔滨医科大学附属第一医院32例APL患者,用逆转录-聚合酶链反应(RT-PCR)检测人肺组织基质细胞衍生子(SDF-1α)的表达,用流式细胞术检测亚砷酸(ATO)诱导分化的APL(APL/ATO)CXCR4的表达,用微重力旋转培养系统进行APL/ATO浸润人肺组织的体外试验,观察地塞米松(Dex)、阿糖胞苷(Ara-C)和柔红霉素(DNR)对APL/ATO粘附、迁移和浸润能力的影响。结果APL/ATO可明显浸润正常人肺组织,APL/ATO表面CXCR4表达平均荧光强度(MFI)为28.77±1.05明显高于诱导前APL的9.20±4.14。与对照组相比,Dex组可明显抑制APL/ATO的粘附和迁移能力[(29.91±2.70)%对(48.20±5.00)%;30.01±5.01对60.10±3.02];与对照组比较,AraC组和DNR组可明显抑制APL/ATO的粘附、迁移和浸润能力[(30.10±3.00)%、(32.20±2.20)%对(48.20±5.00)%;28.01±5.00、24.02±4.01对60.10±3.02;18.20±3.56、16.01±3.25对46.01±4.05]。结论CXCR4和(或)SDF-1α的高表达可能是APL/ATO引起肺浸润和维甲酸综合征的分子机制之一,Dex、AraC和DNR可抑制APL/ATO的粘附、迁移和浸润。

Objective To explore the molecular pathological mechanism and treatment of retinoic acid syndrome（RAS）. Methods SDF-1α of health adult lung was measured by RT-PCR,CXCR4 on the cell membrane of APL specialized by arsenic trioxide（APL/ATO） were tested by FCM ,and we used the rotary cell culture system（RCCS） to build the model of simulated experiment in vitro of APL/ATO infiltrating into the human lung;observe if Dex, Ara-C and DNR can influence the ability of APL/ATO in adhesion,transplantation and infiltration. Results The APL/ATO could evidently infiltrate in- to human lung, mean fluorescence intensity （MFI） of CXCR4 on the cell membrane of APL/ATO was 28. 77 ± 1.05, which was much higher than the unspecialized APL（9. 20 ±4. 14）. Contrast to control cells,Dex could dramatically restrain the ability of APL/ATO in adhesion and transference [ （29. 91 ±2.70）% vs（48.20 ±5.00）% ,30.01 ±5.01 vs 60. 10 ± 3.02 ], while Ara-C and DNR could distinctly depress the ability of APL/ATO in adhesion, transplantation and infiltration [（30.10±3.00）%, （32.20±2.20）% vs（48.20±5.00）%;28.01 ±5.00,24.02±4.01 vs60.10±3.02;18.20± 3.56,16.01 ±3.25 vs 46. 01 ± 4.05 ]. Conclusion High expression of CXCR4 on APL/ATO and SDF-1α in the lung may be one of the molecular mechanism of the lung infiltration and RAS;DEX,Ara-C and DNR can restrain the ability of APL/ATO in adhesion,transplantation and infiltration.