系统性红斑狼疮单核细胞中转录因子STAT1 DNA结合活性的研究

Investigation of the DNA-binding activity of signal transducer and activator of transcription 1(STAT1) from monocytes of patients with systemic lupns erythematosus(SLE)

目的探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)患者外周血单核细胞核蛋白中可与序列特异DNA结合、具有基因调控能力的转录因子STAT1(signal transducer and activator of transcription 1,STAT1)的DNA结合活性和含量。方法对7例活动期SLE患者,6例病情稳定期SLE患者及8例健康人,采用凝胶滞留法(electrophoretic mobility shift assay,EMSA)检测外周血单核细胞核蛋白中转录因子STAT1的DNA结合活性,并对其进行定量。结果所有SLE患者外周血单核细胞核蛋白中转录因子STAT1的DNA结合活性和含量明显增高(P<0．05)。活动期SLE患者组外周血单核细胞核蛋白中转录因子STAT1的DNA结合活性和含量明显高于稳定期SLE患者组和正常人对照组(P<0．01)。稳定期SLE患者组也显著高于正常人对照组(P<0．05)。经统计学检验,转录因子STAT1的DNA结合活性和含量与患者的抗核抗体滴度、血沉相关;与补体C3浓度负相关;不与SLE疾病活动评分相关。结论SLE患者组外周血单核细胞核蛋白中转录因子STAT1的DNA结合活性和含量显著增高,这一结果提示转录因子STAT1的DNA结合活性的异常增强与SLE的发病有关。

Objective To investigate the amount and DNA-binding activity of signal transducer and activator of transcription 1（STAT1） in the nuclear extracts from monocytes of patients with systemic lupus erythematosus（SLE）. Methods Seven active SLE patients, six remission SLE patients and eight health controls were included. The DNA-binding activity of STAT1 was examined by electrophoretic mobility shift assays（EMSA）. Resuits The DNA-binding activity of transcription factor STAT1 significantly higher in all patients with SLE（ P 〈 0.05 ）. In controls, only two persons showed faint transcription factor STAT1 positive. The DNA-binding activity of transcription factor STAT1 of active SLE patient group was 2 to 4 fold to that of remission SLE patients（ P 〈 0.01 ）, and the DNA-binding activity of transcription factor STAT1 of remission SLE patient group were 3 to 8 fold to that of health controls （ P 〈 0.05）. There exist significant differences among the three groups. The DNA-binding activity of transcription factor STAT1 correlated with erythrocyte sedimentation rate （ESR） and anti-dsDNA antibody titers; there was a negative correlation between the DNA-binding activity of transcription factor STAT1 and the titer of complement 3. No correlation was found between DNA-binding activity of transcription factor STAT1 and SLE DAI. Conclusion DNA-binding activity of transcription factor STAT1 was enhanced in patients with SLE, so it was suggested that the increase of DNA-binding activity of transcription factor STAT1 could be involved in the pathogenesis of SLE.