维生素D及其受体在强直性脊柱炎患者中的表达及其临床意义

Clinical significance of vitamin D and vitamin D receptor in patients with ankylosing spondylitis

目的:研究AS患者PBMC维生素D受体(VDR)mRNA的表达及血清25-羟维生素D3和1,25-二羟维生素D3的水平,探讨其与AS疾病活动性(BASDAI、CRP、ESR)的相关性。方法:选取26例AS患者(AS组)和年龄、性别与之相匹配的13名健康志愿者(健康对照组)。采用SYBR GreenⅠ实时荧光定量PCR检测两组受检者PBMC的VDR mRNA表达水平,应用ELISA法检测两组受检者血清25-羟维生素D3和1,25-二羟维生素D3水平,分析VDR mRNA表达水平、血清25-羟维生素D3和1,25-二羟维生素D3水平与临床相关指标(BASDAI、CRP、ESR)的关系。结果:AS患者PBMC的VDR mRNA表达水平明显高于健康对照组(P<0.01),VDR mRNA表达水平与临床相关指标(BASDAI、CRP、ESR)无关(P>0.05)。AS患者血清25-羟维生素D3、1,25-二羟维生素D3水平分别为(5.3±2.6)μg/L、(12.8±6.0)ng/L,明显低于健康对照组(14.7±3.5)μg/L、(32.6±18.5)ng/L(P均<0.01)。AS患者血清1,25-二羟维生素D3的水平与BASDAI(r=-0.481,P<0.05)、ESR(r=-0.535,P<0.01)、CRP(r=-0.674,P<0.01)均呈负相关。血清25-羟维生素D3水平与BASDAI、CRP、ESR无关(P>0.05)。结论:AS患者VDR mRNA表达水平升高,但与AS的疾病活动无关。AS患者血清1,25-二羟维生素D3水平下降,与疾病活动呈负相关,可作为AS疾病活动的指标之一。AS患者PBMC的VDR活化可能与1,25-二羟维生素D3的作用无关。

Objective： To study the expression of vitamin D receptor （VDR） mRNA in peripheral blood mono- cytes of patients with Ankylosing Spondylitis （AS） and explore the correlation between the disease activity [ eryth- roeyte sedimentation rate （ESR）, C-reactive protein （CRP）, Bath Ankylosing Spondylitis Disease Activity Index （BASDAI） 1 and the serum levels of 25-hydroxyvitamin D3 [25-D/25- （OH） D31 and 1,25-Dihydroxy vitamin D3 E1, 25-D/1, 25- （OH） 2D3）I in AS patients. Methods： Twentysix patients with AS and 13 age- and sex-matched healthy controls were included. Fieoll density gradient centrifugation method was used to segregate pe- ripheral blood mononuelear cells. Subsequently, total RNA in isolated monoeytes was extracted by Trizol and re- verse transeripted into eDNA. The VDR mRNA expression was examined by real time fluorescent quantitative re- verse transcriptase polymerase chain reaction （real-time qRT-PCR） and quantified using the 2-A ACT method. The serum levels of 25-D and 1, 25-D were measured by enzyme linked immuno-sorbent assay （ELISA）. The eor- relations between disease activity （ESR, CRP and BASDAI） and expression of VDR mRNA and serum levels of 25-D and 1, 25-D were evaluated by spearman＇s rank correlation analysis. Results： The expression of VDR mRNA was significantly higher in AS group than that in control group （ P 〈 0.01 ）. There was no signifieant eorrelation between expression of VDR mRNA and disease activity （BASDAI, ESR and CRP） （P 〉0. 05）. The concentrations of 25-D and 1, 25-D were in AS group were significantly lower than those in healthy controls [ L vs （ 14.7±3.5 ）μg/L and （ 12.8± 6.0）ng/L vs （32. 6±18.5 ）ng/L, P 〈 0. 01 ]. In AS group, tive correlations were found between 1, 25-D and BASDAI （ r = - 0. 481, P 〈 0. 05 ） , ESR （ r 0. 01） and CRP （r = -0. 674, P 〈0. 01 ）. However, there was no significant correlation was （5.3 ±2.6）μg/ significant nega- = -0.535, P〈 revealed between serum 25-D level and BASDAI, ESR or CRP in patients with AS （P 〉 0.05 ）. Conclusion： Increased expression of VDR mRNA in AS patients has no correlation with the disease activity. The reduction of 25-D and 1, 25-D neg- atively correlated with disease activity of AS. Thus serum level of 1, 25-Dihydroxy vitamin D can be used as an in- dicator for disease activity of AS. The VDR activation may not relate to 1, 25-D.