类风湿关节炎患者血清骨代谢标志物水平及炎症因子变化研究

The study on bone me tabolism and change s of inflammatory factors in patie nts with rhe umatoid arthritis

目的探讨类风湿关节炎(rheumatoid arthritis,RA)患者血清骨代谢标志物水平及炎症因子的变化。方法收集RA患者60例和健康对照者20名,再将60例RA患者按照是否合并骨质疏松(osteoporosis,OP)分为OP组(32例)和非OP组(28例)。采用双能X射线骨密度测量仪测骨密度,酶联免疫吸附法测定外周血清白细胞介素(interleukin,IL)-1β、IL-6、IL-17、I型前胶原N-末端前肽(N-terminal propeptide of type I collagen,PINP)、I型胶原C-末端交联顶端肽(type I collagen cross-linked Ctelopeptide,CTX)水平,并详细记录临床、实验室资料。对两组间计量资料采取独立样本t检验进行比较,采用Pearson积差相关法进行相关性分析。结果 (1)RA组与对照组相比,其骨密度、PINP水平普遍较低(P<0.05);CTX、IL-1β、IL-17、IL-6水平普遍较高(P<0.05)。(2)与非OP组相比,OP组的年龄、病程、IL-1β、IL-17、IL-6水平普遍较高(P<0.05),OP组患者CTX、PINP水平虽然高于非OP组,但差异无统计学意义(P>0.05)。(3)RA患者外周血血清中IL-1β与红细胞沉降率(erythrocyte sedimentation rate,ESR)成正相关(r=0.423,P<0.05),IL-6与C反应蛋白(C-reactive protein,CRP)、ESR、类风湿关节炎患者病情评价(DAS28评分)成正相关(r=0.473、0.370、0.481,P<0.05);IL-17与CRP、ESR、DAS28成正相关(r=0.411、0.367、0.468,P<0.05);CTX与疾病活动性指标CRP、ESR、DAS28呈正相关(r=0.536、0.488、0.466,P<0.05),与病程呈负相关(r=-0.268,P<0.05);PINP水平与各疾病活动性指标间均无相关性(P>0.05)。结论 RA患者存在较高的OP发生率,且合并OP患者IL-1β、IL-17、IL-6高于未合并OP患者,RA患者中继发OP作用机制可能与炎症因子IL-1β、IL-6、IL-17相关;CTX和PINP与疾病活动和OP密切相关,测定这两个骨代谢指标能够了解RA患者早期骨破坏程度。

Objective To investigate the levels of serum bone metabolic markers and inflammatory factors in patients with rheumatoid arthritis. Methods A total of 60 RA patients and 20 healthy controls were enrolled into this study. According to whether associated with osteoporosis,a total of 60 rheumatoid arthritis patients were divided into OP group（ n = 32） and NOP group（ n = 28）. Bone mineral density（ BMD） was measured by dual energy X-ray absorptiometry. The level of IL-1β,IL-6,IL-17,PINP,CTX,OPG and IL-6 were detected by ELISA. Relevant clinical and laboratory data were also recorded. T-test was used for data analysis,and Pearson＇s test was adopted for correlation analysis. Results（1）Compared with the controls,the levels of BMD and PINP in RA patients decreased significantly,whereas the levels of CTX,IL-1β,IL-17 and IL-6 increased significantly（ P〈0. 05）.（2）Compared with the NOP group,the levels of IL-1β,IL-17 and IL-6 increased significantly in the OP group（ P〈0. 05）.The levels of CTX and PINP in the OP group were higher than those in the non-OP group but there was no statistical differencebetween two groups.（3）The level of IL-1β was positively correlated with ESR（ r = 0. 423,P〈0. 05）. The level of IL-6 was positively correlated with CRP,ESR and DAS28（ r = 0. 473,0. 370,0. 481,P〈0. 05）. The level of IL-17 was positively correlated with CRP,ESR and DAS28（ r = 0. 411,0. 367,0. 468,P〈0. 05）. The level of CTX was positively correlated with CRP,ESR and DAS28（ r = 0. 536,0. 488,0. 466,P〈0. 05）,but negatively correlated with the course of disease（ r =-0. 268,P〈0. 05）. PINP was not statistically different between two groups（ P〈0. 05）. Conclusion RA patients had a higher incidence of OP,and the levels of IL-1β,IL-17 and IL-6 were higher in OP patients than NOP patients. The levels of CTX,as well as PINP ratio correlated with disease activity and secondary osteoporosis in RA. These two bone metabolic markers can be used to understand the extent of bone destruction in patients with RA.