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目的探讨趋化因子CXCL16及其受体CXCR6(CXCL16/CXCR6)在强直性脊柱炎(AS)发病中的作用机制,及重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rh TNFR:Fc)的作用机制。方法实验分为AS活动组、AS治疗组及健康对照组,用酶联免疫吸附试验(ELISA)和荧光定量PCR法分别检测血清细胞核因子-κB受体活化因子配体(RANKL)、骨保护素(OPG)、CXCLl6水平及外周血单个核细胞(PBMC)CXCL16、CXCR6 mRNA表达水平;采用CCK-8法和ELISA法分别检测不同浓度CXCLl6重组蛋白(40、80 ng/m L)刺激淋巴细胞的增殖及培养上清中RANKL的表达水平。结果 1AS活动组经rh TNFR:Fc治疗后,临床效果达95.45%,且AS治疗组各疗效指标血沉(ESR)、C反应蛋白(CRP)、Bath AS活动指数(BASDAI)、Bath AS功能指数(BASFI)、脊柱痛、夜间痛均较AS活动组下降(P均<0.05);2 AS活动组RANK水平、RANKL/OPG比值均高于健康对照组(P均<0.05);AS活动组血清CXCL16的表达及PBM C之CXCL16、CXCR6 mRNA的表达均高于健康对照组及AS治疗组(P均<0.05);3在CXCLl6(40、80 ng/m L)刺激下,AS活动组淋巴细胞增殖能力高于无CXCLl6组(P均<0.05),且培养上清中RANKL表达水平高于无CXC Ll6组(P均<0.05);4 AS活动组血清CXCL16与RANKL、RANKL/OPG比值及ESR、CRP等实验室指标呈正相关(P均<0.05)。结论 CXCL16/CXCR6在AS的发病中可能发挥着重要作用,且rh TNFR:Fc降低CXCL16/CXCR6的表达可能是其抑制AS炎症反应及骨质破坏的重要作用机制之一。
Objective To investigate the mechanism of the chemokine CXCL16 and its receptor CXCR6 (CXCL16 / CXCR6) in the pathogenesis of ankylosing spondylitis (AS) and the effect of recombinant human TNF-α (TNFR) The mechanism of action. Methods The experimental groups were divided into AS group, AS group and healthy control group. Serum levels of nuclear factor-kappa B receptor activator ligand (RANKL), osteoprotegerin (OPG), CXCL16 levels and the expression of CXCL16 and CXCR6 mRNA in peripheral blood mononuclear cells (PBMC). The expressions of CXCL16 and CXCR6 mRNA were detected by CCK-8 assay and ELISA assay Proliferation and culture supernatants RANKL expression levels. Results After treatment with rh TNFR: Fc, the clinical effect of 1AS was 95.45%, and the indexes of ESR, CRP, BASDAI, Bath AS function index ( BASFI), spinal pain and nocturnal pain decreased compared with those in AS group (all P <0.05). The levels of RANK and RANKL / OPG in 2 AS group were significantly higher than those in healthy control group (all P <0.05) (P <0.05) .3 The expressions of CXCL16 and CXCR6 mRNA in PBM C were significantly higher than those in healthy control and AS (P <0.05) (P <0.05). The expression level of RANKL in culture supernatant was higher than that in the control group without CXC Ll6 (all P <0.05). The serum levels of CXCL16, RANKL, RANKL / OPG and ESR, CRP and other laboratory indicators were positively correlated (P all <0.05). Conclusion CXCL16 / CXCR6 may play an important role in the pathogenesis of AS, and the decrease of CXCL16 / CXCR6 expression by rh TNFR: Fc may be one of its important mechanisms of inhibiting AS inflammatory reaction and bone destruction.