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脂多糖对人类风湿性关节炎滑膜细胞基质金属蛋白酶-9表达的影响

Effect of lipopolysaccharide on expression of matrix metalloproteinase-9 in human synoviocyte from patients with rheumatoid arthritis

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【作者】 刘柏合李怡棠沈放赵丹阳程桂芳

【Author】 LIU Bai he 1, LI Yi tang 1, SHEN Fang 1, ZHAO Dan yang 2, CHENG Gui fang 1* (1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; 2. Department of Kidney Diseases, Beijing Integrated Traditional and Western Hospital, Beijing 100039, China)

【机构】 中国医学科学院、中国协和医科大学药物研究所北京市中西医结合医院中国医学科学院、中国协和医科大学药物研究所 北京100050北京100050北京100039北京100050

【摘要】 目的 研究脂多糖 (LPS)对人类风湿性关节炎 (RA)成纤维状滑膜细胞 (FLS)基质金属蛋白酶 9(MMP 9)表达的影响。方法 明胶酶谱法测定MMP 9酶活性 ;Westernblot法测定MMP 9蛋白的表达 ;RT PCR法测定MMP 9mRNA的表达。结果 LPS处理对FLS中MMP 9表达无显著影响 ;LPS刺激的U93 7细胞培养上清液可明显增强FLS中MMP 9酶活性、蛋白分泌及mRNA表达 ;地塞米松可显著抑制上述变化 ,且其抑制作用随浓度的增加而增强。结论 LPS对FLS中MMP 9表达无直接影响 ,LPS刺激的U93 7细胞上清液使FLS中MMP 9表达增加 ,而地塞米松能抑制MMP 9的变化

【Abstract】 Aim To study the effects of lipopolysaccharide (LPS),the supernatant of U937 cells stimulated with LPS and dexamethasone on matrix metalloproteinase 9 (MMP 9) expression in the synoviocyte from patients with rheumatoid arthritis(RA). Methods Fibroblast like cells (FLS) from the joint tissue of patients with rheumatoid arthritis were cultured and incubated for 24 h with LPS (1 mg·L -1 ) or the supernatant of U937 cells stimulated with LPS (1 mg·L -1 ) for 24 h. Dexamethasone was added to the supernatant of U937 cells and FLS was incubated for 24 h. The activity of MMP 9 was analyzed by gelatin zymography. Protein expression of MMP 9 was detected by Western blot using special polyclonal antibodies. The mRNA expression of MMP 9 was detected by RT PCR. Results The expression of MMP 9 was not markedly changed in FLS treated with LPS. The MMP 9 activity, MMP 9 secretion and MMP 9 mRNA expression were significantly increased in FLS cultured with the supernatant from U937 cell treated with LPS. Dexamethasone markedly inhibited the activity, protein secretion and mRNA expression of MMP 9 in FLS cultured with the supernatant from U937 cell stimulated with LPS, and the inhibitory effects were increased as the concentration of dexamethasone increased.Conclusion LPS did not directly affect the expression of MMP 9 in FLS, but it was found to indirectly cause the increase of MMP 9 expression in FLS by stimulating U937 cell. Dexamethasone was found to inhibit this increase of MMP 9 expression.

  • 【文献出处】 药学学报 ,Acta Pharmaceutica Sinica , 编辑部邮箱 ,2003年04期
  • 【分类号】R593.22
  • 【下载频次】131
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