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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 study the expression of BMP / Smads signaling pathway related genes in patients with systemic lupus erythematosus (SLE) and to investigate their correlation with OPG / RANKL and its significance in bone metabolism of SLE. Methods: Twenty-six patients with SLE and 20 normal controls were enrolled. The expression of BMP-2, Smad1, Smad5, Smad8, RANKL and OPG in peripheral blood mononuclear cells were detected by real-time PCR. Serum levels of RANKL and OPG were measured by ELISA, and the ratio of OPG / RANKL was calculated. The expression of Smad1, Smad5 and Smad8 were analyzed with correlation with disease activity and OPG / RANKL. Results: The expression of OPG m RNA in OPG / RANKL system of SLE patients was significantly lower than that of the normal controls (0.002 5 ± 0.000 7 vs 0.017 6 ± 0.006 7, P <0.05) The statistical difference (0.003 3 ± 0.001 0 vs.0.002 4 ± 0.000 9, P> 0.05), SLE patients OPG / RANKL ratio was significantly lower than the normal control group (0.229 6 ± 0.071 2 vs.0.609 5 ± 0.165 1, P < 0.01). SLE patients with Smad1, Smad8 gene m RNA expression levels were significantly lower than the normal control group (0.003 1 ± 0.000 4 vs.00.006 6 ± 0.000 7; 0.003 3 ± 0.000 5 vs.0.005 6 ± 0.000 6, P <0.01), Smad5 gene m RNA expression in SLE patients was lower than that in control group (0.001 7 ± 0.000 3 vs 0.04 2 ± 0.000 4, P <0.05). There was no significant difference in m RNA expression between SLE patients and normal controls (0.006 9 ± 0.002 0 vs.0.010 5 ± 0.002 1, P> 0.05). The level of RANKL in serum of SLE patients was significantly higher than that of normal controls (P <0.01), and the expression of OPG was not significantly different between the two groups (P> 0.05). The SLE serum OPG / RANKL levels were significantly lower than those of normal controls (P = 0.006 ). Correlation analysis showed that SLE patients with Smad8mRNA levels, OPG / RANKL were positively correlated with erythrocyte sedimentation rate (P <0.05). The mRNA level of OPG was positively correlated with the expression of Smad8 mRNA (P <0.01), but negatively correlated with the expression of Smad1 mRNA (P <0.01). Conclusion: The abnormal gene expression of BMP / Smads system in SLE patients may be related to abnormal bone metabolism in SLE.