目的 :研究系统性红斑狼疮(SLE)患者外周血BMP/Smads信号通路相关基因表达,了解其与OPG/RANKL相关性,探讨其在SLE骨代谢中的意义。方法:选取SLE患者26例及正常对照组20例,运用实时定量PCR方法检测两组外周血单个核细胞BMP/Smads信号通路相关基因BMP-2、Smad1、Smad5、Smad8及RANKL、OPG的表达,ELISA法定量检测血清中RANKL、OPG水平,计算OPG/RANKL比值;分析Smad1、Smad5、Smad8基因表达量与疾病活动相关指标及OPG/RANKL相关性。结果:SLE患者外周血单个核细胞OPG/RANKL系统中OPG基因m RNA表达水平较正常对照组减低(0.002 5±0.000 7vs.0.017 6±0.006 7,P〈0.05),RANKL基因m RNA表达水平无统计学差异(0.003 3±0.001 0 vs.0.002 4±0.000 9,P〉0.05),SLE患者OPG/RANKL比值较正常对照组明显减低(0.229 6±0.071 2 vs.0.609 5±0.165 1,P〈0.01)。SLE患者Smad1、Smad8基因m RNA表达水平较正常对照组明显减低(0.003 1±0.000 4 vs.0.006 6±0.000 7;0.003 3±0.000 5 vs.0.005 6±0.000 6,P〈0.01),Smad5基因m RNA表达较正常对照组减低(0.001 7±0.000 3 vs.0.004 2±0.000 4,P〈0.05),SLE患者与正常对照组BMP-2基因m RNA表达水平无统计学差异(0.006 9±0.002 0 vs.0.010 5±0.002 1,P〉0.05)。SLE患者组血清RANKL表达较正常对照组明显增高(P〈0.01),OPG表达在两者间无明显统计学意义(P〉0.05),SLE血清OPG/RANKL较正常对照组明显减低(P=0.006)。相关性分析显示,SLE患者Smad8 m RNA水平、OPG/RANKL均与血沉呈正相关(P〈0.05)。OPG m RNA水平与Smad8 m RNA表达水平呈正相关P〈0.01,而RANKL与Smad1 m RNA基因表达呈负相关(P〈0.01)。结论 :SLE患者体内BMP/Smads系统基因表达存在异常,可能与SLE的骨代谢异常相关。
Objective: To detect the m RNA levels of genes of BMP / Samd signaling pathway in peripheral blood mononuclear cells of patients with systemic lupus erythematosus(SLE) and to determine their correlations with the ratio of OPG / RANKL, thus to further investigate the effect of BMP / Smad pathway on the bone metabolism of SLE patients. Methods: The m RNA levels of RANKL, OPG, BMP-2 and Smad1 / 5 / 8 gene in peripheral peripheral blood mononuclear cells from 26 SLE patients and 20 normal controls were detected by rea1-time PCR(RT-PCR), and the protein level of OPG and RANKL were measured by ELISA. The correlation analysis between these genes of BMP / Smad signaling and the ratio of OPG / RANKL or some indexes of disease activity were studied. Results: The m RNA levels of OPG decreased in SLE patients compared with normal controls(0.002 5 ± 0.000 7 vs.0.017 6 ± 0.006 7, P 〈 0.05), and RANKL levels had no differences between the two groups(0.003 3 ± 0.001 0 vs. 0.002 4 ± 0.000 9,P 〉 0.05), which led to a decreased ratio of OPG / RANKL(0.229 6 ± 0.071 2 vs. 0.609 5 ± 0.165 1, P 〈 0.01). Both the m RNA levels of Smad1 and Smad8 were significantly decreased in SLE patients than those in controls(0.003 1 ± 0.000 4 vs. 0.006 6 ± 0.0007; 0.003 3 ± 0.000 5 vs. 0.005 6 ± 0.000 6,P 〈0.01), and also the level of Smad5 was decreased(0.001 7 ± 0.000 3 vs. 0.004 2 ±0.000 4, P 〈 0.05). There were no differences on the BMP-2 gene expression between the two groups(0.006 9 ± 0.002 0 vs. 0.010 5± 0.002 1,P 〉 0.05). Serum protein levels of RANKL were higher in SLE patients than those in controls(P 〈 0.01), while OPG levels had no differences between the two groups, which led to an decreased ratio of OPG / RANKL(P = 0.006) in SLE patients. Analysis showed that positive correlation between m RNA level of Smad8, ratio of OPG / RANKL and ESR levels of SLE patients(P 〈 0.05).Moreover, m RNA levels of Smad8 and OPG were found positively related(P 〈 0.01), wh