依那西普治疗强直性脊柱炎临床疗效及对Dickkopf-1硬化素及OPG表达的影响

目的探讨依那西普治疗强直性脊柱炎(AS)疗效及对Dickkopf-1(DKK-1)、硬化素、骨保护素(OPG)、NF-κB受体活化因子配体(RANKL)表达影响.方法60例AS患者随机分为依那西普治疗组(27例,脱落3例)和柳氮磺吡啶治疗组(28例,脱落2例),疗程均为12周.比较治疗前后两组患者BASDAI、ESR、CRP水平及血清DKK-1、OPG、硬化素及RANKL水平.结果治疗12周后,依那西普组BASDAI、ESR、CRP及RANKL分别为[(2.33±0.93)、(27.00±18.11)mm/h、(17.44±7.75)mg/L及(73.49±11.88)pg/ml]均较治疗前[(5.94±1.06)、(65.11±29.33)mm/h、(50.41±20.36)mg/L及(94.54±12.99)pg/ml]明显下降,差异有统计学意义(P<0.05),OPG[(107.71±17.39)pg/ml VS.(138.38±15.36)pg/ml]明显上升(P<0.05),而DKK-1[(193.53±22.46)pg/mlVS.(170.89±22.36)pg/ml]及硬化素[(0.65±0.11)pg/mlVS.(0.64±0.11)pg/ml]水平无明显改变(P>0.05).柳氮磺吡啶组BASDAI、CRP及ESR均较治疗前明显下降(P<0.05),OPG、RANKL、DKK-1、硬化素前后差异无统计学意义(P>0.05).治疗12周后,依那西普组BASDAI、CRP、ESR、DKK-1及RANKL水平较柳氮磺吡啶组明显下降(P<0.05),OPG水平显著上升(P<0.05)、硬化素水平两组比较差异无统计学意义(P>0.05).DKK-1水平与BASDAI、CRP、ESR、OPG、RANKL均无相关性(P>0.05),与硬化素水平明显相关(P<0.05).结论依那西普组较柳氮磺吡啶组可显著改善AS临床症状,且能下调RANKL表达,上调OPG表达,改善骨质破坏,但对DKK-1及硬化素水平无明显影响.

Objective To explore the effect of Etanercept on ankylosing spondylitis(AS)and its influence on dickkopf-1(DKK-1),sclerostin,osteoprotegerin(OPG)and receptor activator of nuclear factor-κB ligand(RANKL),compared with sulfasalazine(SSZ).Methods Sixty AS patients were randomly divided into 2 groups:the etanercept group(27cases,3cases lost)and the SSZ group(28cases,2cases lost).Markers of bone remodelling and inflammation were assessed at baseline and after 3 months.Results In the TNF-αinhibitor treatment group BASDAI,ESR,CRP and RANKL decreased significantly from[(5.94±1.06),(65.11±29.33)mm/h,(50.41±20.36)mg/L and(94.54±12.99)pg/ml]to[(2.33±0.93),(27.00±18.11)mm/h,(17.44±7.75)mg/L and(73.49±11.88)pg/ml]respectively,and the differences were statistically significant(P<0.05),OPG increased significantly from(107.71±17.39)pg/ml to(138.38±15.36)pg/ml(P<0.05),but the changes of DKK-1(193.53±22.46 vs 170.89±22.36)pg/ml and sclerostin(0.65±0.11 vs 0.64±0.11)pg/ml were not statistically significant(P>0.05).In the SSZ group the BASDAI,ESR and CRP decreased significantly from[(5.95±0.94),(61.54±18.47)mm/h,(50.96±18.47)mg/l]to[(4.98±0.94),(39.14±20.74)mm/h,(39.50±16.48)mg/l](all P<0.05),but the changes of DKK-1,sclerostin,OPG and RANKL were not significant(P>0.05).The indexes of BASDAI,CRP,ESR,RANKL,DKK-1 in patients of the etanercept group were significantly decreased than patients of the SSZ group after 3 months’treatment(P<0.05).While the index of OPG was significantly increased(P<0.05).There were no relations between DKK-1 and BASDAI,ESR,CRP,OPG and RANKL,all P>0.05.Conclusion Compared with SSZ,etanercept may improve the clinical indicators and inflammation significantly,and may change bone remodel pattern through OPG/RANK/RANKL system,instead of Wnt pathway.