维生素D对活动期系统性红斑狼疮患者内皮祖细胞的影响

摘要

目的:观察活动期系统性红斑狼疮(SLE)患者内皮祖细胞(EPCs)数量及功能的变化,并探讨维生素D对SLE患者EPCs数量及功能的影响.方法:收集30例SLEDAI评分大于8分,病情均处于活动期的SLE患者,30例年龄与性别匹配的健康人作为正常对照;酶联免疫吸附试验(ELISA)检测外周血25羟基维生素D[25(OH)D]水平;密度梯度离心和贴壁培养法分离培养EPCs,流式细胞术检测CD34+/VEGFR-2+EPCs在全血中的比例;通过计数再贴壁和构建侵袭小室检测EPCs黏附和迁移能力.结果:①体外培养过程中,活动期SLE患者EPCs数量(0.028±0.017)%显著低于正常对照组(0.067±0.012)%,有统计学差异(P<0.05);②活动期SLE患者EPCs迁移率(1.7±0.9)‰及黏附能力(19±7)显著低于正常对照组EPCs迁移率(3.1±1.6)‰及黏附能力(34±11),有统计学差异(P<0.05);③活动期SLE患者外周血25(OH)D质量浓度(14.47±10.39)ng/mL水平低于健康对照组质量浓度(24.15±7.98)ng/mL,有统计学差异(P<0.05);④25(OH)D能够增加活动期SLE患者EPCs数量(0.045±0.012)%,高于未加25(OH)D组(0.031±0.012)%,有统计学差异(P<0.05);⑤25(OH)D能够增加活动期SLE患者EPCs迁移率(2.6±0.7)‰及黏附能力(24±9),高于未加25(OH)D组迁移率(1.3±0.8)‰及黏附能力(13±6),有统计学差异(P<0.05).结论:SLE患者维生素D水平降低,可诱发Ⅰ型干扰素通路活化,从而导致EPCs数量和/或功能异常,最终造成狼疮患者血管内皮损伤后修复障碍引发动脉粥样硬化.%Objective:To investigate the effects of vitamin D on Endothelial Progenitor Cells from patients with active systemic lupus erythematosus.Methods:Thirty consecutive patients(SLEDAI score≥8)in the active phase of SLE,also in-patients of our Hospital, aged 30 years, were included in the study,and a group of sex-matched healthy people was used as a control.Enyme linked immune sorbent assay(ELISA)was used to determine the level of 25-dihydroxyvitamin D[25(OH)D]in the peripheral blood.Endothelial progenitor cells(EPCs)were isolated by density gradient centrifugation and cultured. CD34 +/VEGFR-2 +EPCs ratios were analyzed by Flow cytometry.Migration and adhesion of EPCs were observed by transwell migration assay.Statistical analysis was conducted with t-test and Mann-Whitney rank test.Results: ① In active SLE subgroups, the number of EPCs(0.028±0.017)% were significantly lower than the normal control(0.067±0.012)%(P<0.05).②The migration rate of EPCs from the active SLE patients(1.7±0.9)‰ was significantly reduced as compared to the normal control(3.1±1.6)‰(P<0.05).Adhesion of EPCs from the active SLE patients(19±7)was declined as compared to the normal control(34±11)(P<0.05).③ The level of peripheral blood 25 (OH)D in patients with active SLE(14.47±10.39)ng/ml was lower than the normal control(24.15±7.98)ng/mL(P<0.05).④25(OH)D caused a significant increase in cell number(0.045±0.012)%of EPCs from the active SLE patients compared to the untreated cells(0.031±0.012)%(P<0.05).⑤25(OH)D caused a significant increase in cell migration(2.6±0.7)‰ and adhesion (24±9)of EPCs from the active SLE patients compared to those of untreated cells,which were(1.3±0.8)‰and(13±6),respectively(P<0.05).Conclusion:Both number and function of EPCs were significantly decreased in SLE patients.Vitamin D may be involved in reduction and dysfunction of EPCs in SLE.