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首页> 中文期刊> 《中华风湿病学杂志》 >骨关节炎软骨细胞和滑膜细胞金属蛋白酶活性的影响因素

骨关节炎软骨细胞和滑膜细胞金属蛋白酶活性的影响因素

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Objective To evaluate the effects of some cytokins,growth factorsand drugs on MMP activities in culture medium of osteoarthritic chondrocytes and synoviocytes.Methods The chondrocyte and synoviocyte monolayer was stimulated with IL-1β,TGF-β1,TNF-α,diclofenac acid,dexamethasone and doxycycline individually for 72 hours.The two kinds of cells were isolated from 10 cases of knee OA cartilage and synovial fluids,respectively.Zymography was used to determine the activities of MMP-2 and -9.Results OA chondrocyte monolayer constitutively produced MMP-2 and -9;but the synoviocytes only produced the MMP-2.MMP-9 activity was markedly reduced by IL-1β,TNF-α and diclofenac.IL-1β was the most effective stimulus and had synergistic effect with TNF-α or diclofenac;but MMP-2 in two kinds of culture media was not affected.Doxcycline,TGF-β1 and dexamethasone could depress the activities of MMP-9 and -2,and antagonized the enhancing effects of IL-1β,TNF-α or diclofenac,thereinto,doxycycline was the most powerful.Conclusion IL-1β1 and TNF-α may be important cytokines degrading OA cartilage,TGF-β1 may be one protective factor,and doxycycline will become one of prospective drugs for OA therapy.%目的 探讨几种细胞因子、生长因子和药物等刺激物对骨关节炎软骨细胞及滑膜细胞金属蛋白酶活性的影响。方法 骨关节炎患者的单层软骨细胞和滑膜细胞均以白细胞介素-1β、转化生长因子-β1、肿瘤坏死因子-α、双氯芬酸钠、多西环素和地塞米松分别处理72h。应用酶谱分析细胞培养上清液中酶活性。结果 单层软骨细胞产生金属蛋白酶-9和-2，而滑膜细胞仅产生金属蛋白酶-2。白细胞介素-1β、肿瘤坏死因子-α和双氯芬酸钠均能显著增强金属蛋白酶-9活性，其中以白细胞介素-1β作用最强，与肿瘤坏死因子-α或双氯芬酸钠有协同作用。多西环素、转化生长因子-β1和地塞米松均能抑制金属蛋白酶-9和-2活性，并与白细胞介素-1β、肿瘤坏死因子-α和双氯芬酸钠起拮抗作用，多西环素为最强的抑制物。结论 白细胞介素-1β和肿瘤坏死因子-α可能为破坏关节软骨的重要细胞因子，转化生长因子-β1则为保护因子，多西环素则可能成为骨关节炎的有效治疗药物。

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