蛋白酪氨酸激酶抑制剂对炎性因子诱导滑膜细胞产生一氧化氮的影响  

The effect of protein tyrosine kinase inhibitor on inflammatory factors induced nitric oxide production in synovial cells

作　　者：王杰松[1] 张俊平[2] 张癸荣[3] 吴久鸿[1] 张俊虎[1] 李勉珊[1] 钱定华[2] 

机构地区：[1]解放军第三○六医院药剂科,北京100101 [2]第二军医大学药学院药理教研室 [3]解放军总后勤部卫生部药品仪器检验所

出　　处：《中华风湿病学杂志》2005年第2期89-91,共3页Chinese Journal of Rheumatology

摘　　要：目的研究炎性因子白细胞介素(IL)-1、肿瘤坏死因子(TNF)和细菌脂多糖(LPS)诱导滑膜细胞产生一氧化氮()的作用以及与蛋白酪氨酸激酶(NOPTK)信号转导通路的关系。方法体外培养兔关节滑膜细胞,IL-1、TNF和LPS单独或联合刺激滑膜细胞,采用Griess方法测定细胞培养液中NO的含量。PTK特异性抑制剂木黄酮、杀莠素A以及具有PTK抑制活性的植物黄酮芹菜素用于考察PTK信号转导通路在滑膜细胞产生NO中的作用。结果譹LPS(1￣100滋g/ml)浓度依赖性地诱导滑膜细胞产生NO,而IL-1仅在1000U/ml才有显著诱导作用,TNF浓度达到1000U/ml仍无任何刺激作用;譺IL-1显著增强LPS诱导滑膜细胞产生NO,TNF对LPS诱导作用则具有较弱的抑制作用;木黄酮(譻6.25￣50.00滋mol/L)浓度依赖性地抑制LPS单独或与IL-1协同诱导滑膜细胞产生NO,而芹菜素和杀莠素A仅有较弱的抑制作用。结论滑膜细胞是除软骨细胞外,NO局部产生的又一重要来源,炎性成分LPS是重要诱导因素之一;IL-1对LPS具有协同作用;滑膜细胞产生NO过程可能有PTK的激活,属于木黄酮敏感性PTK类型。Objective To study the inducible effect of interleukin (IL)-1, tumor necrosis factor (TNF) and lipopolysaccharides (LPS) on nitric oxide (NO) production in synovial cells and the involvement of protein tyrosine kinase (PTK) in this process. Methods Synovial cells cultured in vitro were stimulated by IL-1, TNF, LPS only or in combination. NO in cultured supernatant was assayed by Griess method. Two specific PTK inhibitor genistein and herbimycin A, and apigenin, a flavone with PTK inhibitory effect were applied for detecting the role of PTK signal transduction in the process. Results {1} LPS (1~100 g/ml) dose-dependently induced NO production in synovial cells, IL-1 had significant inducible effect at concentration up to 1000 U/ml, no significant inducible effect was observed in TNF; {2} IL-1 had synergistic action with LPS on NO induction, whereas TNF had a weakly antagonistic effect to LPS; {3} Genistein (6.25~50.00 μmol/L) dose-dependently inhibited NO production in synovial cells induced by LPS only and in combinatμion with IL-1, whereas herbimycin A and apigenin only had weakly inhibitory effect. Conclusion Synovial cells is another reservoir of NO local producer besides chondrocytes. LPS is one of important stimulant and its inducing activity can be enhanction by IL-1. It is possible that PTK kinase involve in the inducing pathway of NO, referring to genistine-sensitive PTK subtype.

关 键 词：蛋白酪氨酸激酶抑制剂 炎性因子 诱导 滑膜细胞 一氧化氮 炎症性关节炎 

分 类 号：R684[医药卫生—骨科学]