注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对强直性脊柱炎患者血清DKK-1及骨代谢指标的影响

目的： 观察注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对强直性脊柱炎（ankylosing spondylitis，AS）患者血清Dickkopf-1蛋白（DKK-1）及骨代谢指标的影响。方法： 选取2016年12月至2018年6月华中科技大学同济医学院附属普爱医院诊治的40名AS患者为AS组，另选取同期40名健康体检者为对照组，所有AS患者均接受注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白25 mg、每周2次皮下注射治疗，疗程24周。比较2组患者外周血清DKK-1、骨代谢指标骨钙素（osteocalcin，OC）、Ⅰ型胶原氨基端前肽（aminoterminal propeptide of type 1 collagen，PINP）、Ⅰ型胶原交联C端肽（C-terminal cross-linking telopeptide of type 1 collagen，CTX-1）]、红细胞沉降率（ESR）和C-反应蛋白（CRP）水平。比较AS组患者治疗前及治疗24周后疾病活动度、白介素-6（IL-6）、肿瘤坏死因子（TNF-α）、DKK-1、骨代谢指标、ESR及CRP水平。分析AS组患者DKK-1及骨代谢指标与疾病活动度、ESR及CRP的关系。结果： AS组患者血清DKK-1水平明显低于对照组（P<0.01），CTX-1、OC及PINP水平高于对照组（P<0.01）。AS组患者治疗24周后，CTX-1、TNF-α、BASDI、ESR及CRP水平均较治疗前明显下降（P<0.01），而DKK-1、IL-6、OC及PINP变化不明显（P>0.05）。AS组患者血清CTX-1水平与ESR、CRP、BASDI水平呈正相关关系，而DKK-1、OC、PINP水平与ESR、CRP、BASDI水平无相关性。结论： AS患者存在骨代谢的紊乱；DKK-1参与AS新骨形成；注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白能有效控制AS炎症，改善骨代谢，但不能上调DKK-1的表达。

Effect of recombinant human tumor necrosis factor-Fc on serum Dkk-1 and bone metabolic parameters in patients with ankylosing spondylitis

OBJECTIVE To explore the therapeutic effect of recombinant human tumor necrosis factor-Fc on ankylosing spondylitis and its effect on serum Dickkopf-1 protein and bone metabolic parameters in patients with ankylosing spondylitis(AS).METHODS Forty AS patients were admitted and treated from December 2016 to June 2018.And another 40 healthy subjects were selected into control group.AS group received recombinant human tumor necrosis factor-Fc,25 mg twice weekly for 24 weeks.The levels of DKK-l,OC,PINP,CTX-1,erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) were compared between two groups.And BASDI,TNF-α,IL-6,DKK-l,bone metabolic parameters,ESR and CRP were compared before and after treatment.The relationships were analyzed between Dkk-1 and bone metabolic parameters with ESR,CRP and BASDAI in AS group.RESULTS The serum level of Dkk-1 was significantly lower in AS group than that in control group(P<0.01).The serum levels of CTX-1,OC and PINP were significantly higher in AS group than those of control group(P<0.01).After 24-week treatment,CTX-1,TNF-α,BASDI,ESR and CRP level decreased markedly nthan those of at baseline in AS group(P<0.01).The serum level of Dkk-1,IL-6,OC and PINP had no statistically significant difference after treatment(P>0.05).In AS group,CTX-1 level was correlated with ESR,CRP and BASDAI.Yet there was no significant relationship between Dkk-1,OC,PINP and pain index.CONCLUSION Bone metabolism disorders occur in AS patients.Dkk-1 may be involved in AS ossification.Recombinant human tumor necrosis factor-Fc reduces the activity of AS disease and improves bone metabolic profiles.However,it fails to up-regulate the expression of DKKl.