【摘要】：背景銀屑病關(guān)節(jié)炎(PsA)有顯著的骨質(zhì)破壞傾向；代謝綜合征在PsA中發(fā)病率很高；脂肪因子(尤其是瘦素和脂聯(lián)素)參與代謝綜合征的發(fā)病,最近研究認為它們同時又在風濕性疾病和骨代謝方面發(fā)揮作用。 目的測量循環(huán)中破骨細胞相關(guān)細胞因子：腫瘤壞死因子-α(TNF-α)、核因子κB受體活化因子配體(RANKL)、骨保護素(OPG)和脂肪因子：瘦素、抵抗素、脂聯(lián)素、趨化素、網(wǎng)膜素濃度,評估其與循環(huán)破骨細胞前體細胞(OCP)水平、影像學評分與疾病活動指數(shù)的關(guān)系,以了解脂肪因子在PsA骨質(zhì)破壞中的意義。 方法PsA患者41例,設(shè)無關(guān)節(jié)炎的銀屑病患者20例,健康志愿者24例為對照。PsA患者采用PsAJAI評估關(guān)節(jié)炎活動度,改良Sharp評分、巴氏放射學指數(shù)(BASRI)評估骨侵蝕情況。取外周血,ELISA法檢測血漿中的TNF-a、RANKL、OPG、瘦素、抵抗素、脂聯(lián)素、趨化素、網(wǎng)膜素濃度。以外周血單個核細胞經(jīng)體外RANKL和巨噬細胞集落刺激因子(M-CSF)刺激后生成的OC計數(shù)來反應(yīng)OCP水平。比較各組的細胞因子和脂肪因子水平及其與骨侵蝕情況和疾病活動指數(shù)的關(guān)系。 結(jié)果與對照組相比,PsA患者血漿TNF-α、RANKL、OCP、瘦素、網(wǎng)膜素濃度較高,而脂聯(lián)素、趨化素、濃度較低。血TNF-α、RANKL、瘦素、網(wǎng)膜素濃度與OCP正相關(guān),而血脂聯(lián)素濃度與OCP負相關(guān)。血TNF-α、RANKL、瘦素與PsAJAI正相關(guān)。TNF-a與影像學評分正相關(guān)。 結(jié)論本研究顯示,PsA患者血漿OCP增加,且存在骨重建相關(guān)的細胞因子及脂肪因子水平的紊亂。PsA患者循環(huán)瘦素、網(wǎng)膜素水平升高,可能有助于關(guān)節(jié)炎骨破壞的發(fā)生。脂肪因子在調(diào)節(jié)PsA骨破壞方面具體機制,有待進一步研究。這可能為臨床治療PsA尋找有效的干預靶點提供依據(jù)。
[Abstract]:Background (PsA) of psoriatic arthritis has a significant tendency to destroy bone; metabolic syndrome is very high in PsA; adipose factors (especially leptin and adiponectin) are involved in the pathogenesis of metabolic syndrome. Recent studies suggest that they also play a role in rheumatic diseases and bone metabolism. Objective to measure the concentrations of osteoclast associated cytokines: tumor necrosis factor- 偽 (TNF- 偽), nuclear factor- 魏 B receptor activator ligand (RANKL), osteoprotegerin (OPG) and fat factors: leptin, resistin, adiponectin, chemotactic factor and omental hormone. To evaluate the relationship between (OCP) level of circulating osteoclast precursor cells, imaging score and disease activity index, and to understand the significance of fat factor in bone destruction of PsA. Methods 41 patients with PsA, 20 patients with psoriasis without arthritis and 24 healthy volunteers were selected as control. PsAJAI was used to evaluate arthritis activity, modified Sharp score and Pap radiology index (BASRI) to evaluate bone erosion in PsA patients. The concentrations of TNF-a,RANKL,OPG, leptin, resistin, adiponectin, chemoattractant and omentin in plasma were determined by ELISA method. The OC count of peripheral blood mononuclear cells stimulated by RANKL and macrophage colony stimulating factor (M-CSF) was used to reflect the OCP level. The levels of cytokines and fat factors in each group and their relationship with bone erosion and disease activity index were compared. Results compared with the control group, plasma TNF- 偽, RANKL,OCP, leptin and omental hormone concentrations in PsA patients were higher, but adiponectin and chemoattractant concentrations were lower. Serum TNF- 偽, RANKL, leptin and omental hormone concentrations were positively correlated with OCP, while serum adiponectin concentrations were negatively correlated with OCP. Serum TNF- 偽, RANKL, leptin were positively correlated with PsAJAI, and TNF-a was positively correlated with imaging score. Conclusion this study showed that plasma OCP increased in patients with PsA, and there was a disturbance of cytokines and fat factors related to bone remodeling. The elevated levels of circulating leptin and omentin in patients with PsA may contribute to the occurrence of bone destruction in arthritis. The specific mechanism of fat factor in regulating PsA bone destruction needs further study. This may provide evidence for clinical treatment of PsA to find effective intervention targets.
【學位授予單位】：復旦大學
【學位級別】：博士
【學位授予年份】：2012
【分類號】：R758.63

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