骨髓基质细胞衍生因子1及其受体在骨髓增生异常综合征患者中的表达  

Expression of stromal cell derived factor-1/CXCR4 biology axis in myelosysplastic syndromes

作　　者：张翼鷟[1] 达万明[2] 赵丹丹[3] 赵海丰[1] 吴晓雄[3] 王卉 

机构地区：[1]天津医科大学附属肿瘤医院血液科,300060 [2]天津医科大学附属肿瘤医院解放军总医院血液科,300060 [3]天津医科大学附属肿瘤医院解放军总医院解放军总医院第一附属医院血液科,300060 [4]北京道陪医院实验室

出　　处：《中华医学杂志》2011年第46期3275-3277,共3页National Medical Journal of China

基　　金：国家自然基金面上项目（30672208）

摘　　要：目的 探讨基质细胞衍生因子1（SDF-1）与其受体趋化因子受体CXCR4在骨髓增生异常综合征（MDS）发病中的可能作用,为MDS的治疗寻找有意义的靶点.方法 收集2006年10月至2010年6月59例MDS病例,根据国际预后积分系统（IPSS）分为低危和高危两组,分别为33例和26例,以10份正常的骨髓标本作为对照.采集骨髓标本,检测骨髓血浆中SDF-1的含量、CD34＋细胞CXCR4的表达率、CD34＋细胞的凋亡率及血管内皮生长因子（VEGF）在骨髓血浆中的表达.结果 SDF-1在低危组和高危组患者骨髓血浆中的含量[（2301±413）、（1173 ±501）ng/L]显著高于对照组[（689±190）ng/L,P＜0.05],低危组显著高于高危组（P＜0.05）.CD34＋细胞CXCR4的表达在高危组（68.1％±18.8％）显著高于低危组（21.0％±9.7％）和对照组（19.4％±5.3％）（P＜0.05）,在后两组的表达率差异无统计学意义（P＞0.05）.CD34＋细胞的凋亡率在低危组、高危组和对照组分别为54.8％±10.2％,24.3％±7.9％,l8.5％±8.7％,前组显著高于后两组（P＜0.05）.骨髓血浆中VEGF的含量在低危组、高危组、对照组分别为（286±97）、（407±168）、（157±46）ng/L,差异有统计学意义（P＜0.05）.相关分析显示：低危组CD34＋细胞的凋亡率与骨髓血浆SDF-1的含量呈正相关（r =0.805,P＜0.05）；高危组血浆VEGF的含量与CD34＋细胞CXCR4的表达呈正相关（r=0.683,P＜0.05）.结论 SDF-1/CXCR4在MDS中存在异常表达,且与骨髓细胞的凋亡和血管新成具有相关性,针对该生物轴的干预可为该病的治疗提供新的靶点.Objective To explore the expression of stromal cell derived factor-1（SDF-1）and its receptor CXCR4 in myelodysplastic symdromes（MDS）.Methods A total of 59 patients with a diagnosis of MDS were divided into low-grade（n =33）and high-grade（n =26）groups according to international prognostic scoring system（IPSS）.Bone marrow（BM）samples were collected.The SDF-1 and VEGF levels in BM plasma,CXCR4 expression on BM CD34 ＋ cell and the apoptosis of CD34 ＋ cells were measured.Results The SDF-1 levels in MDS patients were significantly higher than those of normal controls [（689 ± 190）ng/L,P 〈0.05].And the low-grade group was significantly higher than that of high-grade group[（2301 ± 413）vs（1173 ± 501）ng/L].CXCR4 expression on CD34 ＋ cells were significantly higher in high-grade group（68.1% ± 18.8%）than that of both low-grade（21.0% ± 9.7%）and control groups （19.4% ± 5.3%）（P 〈 0.05）.Apoptotic rate of CD34 ＋ cells were 54.8% ± 10.2% in low-grade group,24.3% ±7.9% in high-grade group and 18.5% ±8.7% in control group.It significantly increased in lowgrade group versus other groups（P 〈0.05）.VEGF levels were significantly higher in MDS patients in lowgrade group[（286 ±97）ng/L]and high-grade group[（407 ± 168）ng/L]versus control group[（157 ±46）ng/L,P 〈0.05].A positive correlation was found between apoptosis of CD34 ＋ cells and SDF-1 levels in low-grade group（r =0.805,P 〈 0.05）,VEGF levels and CXCR4 expression rate in high-grade group（r =0.683 P 〈 0.05）.Conclusion The exnression of SDF-1/CXCR4 is significantly abnormal in MDSpatients.And it is correlated with apoptosis and angiogenesis.Intervention of SDF-1/CXCR4 axis may provide a new therapeutic target.

关 键 词：骨髓增生异常综合征 受体 CXCR4 细胞凋亡 血管内皮生长因子类 基质 细胞衍生因子1 

分 类 号：R551.3[医药卫生—血液循环系统疾病]