依那西普对磨屑诱导骨溶解影响的实验研究

Experimerntal study of etanercept effects the wear debris-induced osteolysis

[目的]检测依那西普(Etanercept,Enbrel)对钛颗粒刺激巨噬细胞(macrophages,MΦ)分泌肿瘤坏死因子α(tumornecrosis factor-α,TNF-α)、白介素1(interleukin-1,IL-1)、白介素6(interleukin-6,IL-6)的影响,探讨依那西普防治人工关节无菌性松动的可能性。[方法]分离、培养小鼠腹腔巨噬细胞,24h后分为5组。A组:仅为MΦ;B组:MΦ+钛颗粒;C组:MΦ+钛颗粒+依那西普(10ng/ml);D组:MΦ+钛颗粒+依那西普(100ng/ml);E组:MΦ+钛颗粒+依那西普(1000ng/ml)。培养18h后,用酶联免疫法(ELISA)检测细胞培养上清液中TNF-α、IL-1、IL-6的含量。[结果]B组TNF-α、IL-1、IL-6含量明显高于A、D、E组(P<0.001),E组TNF-α、IL-1、IL-6的含量明显低于B组、C组(P<0.001,E组和D组间无统计学意义(P>0.05)。[结论]钛颗粒可以刺激MΦ分泌大量的TNF-α、IL-1、IL-6,依那西普能够呈剂量依赖型地有效抑制钛颗粒诱导的MΦ分泌TNF-α、IL-1、IL-6,有望成为预防人工关节无菌性松动的药物。

[ Objective] To detect the effect of Etanercept on the Ti particles induced TNF-α IL - 1 and IL - 6 production by macrophage and to evaluate the validity of the etanercept on treatment of aseptic loosening of prosthesis. [ MФthod] Separate and Cultivate mouse peritoneal macrophages were divide into 5 groups after 24 h. Group A was treated with MФ alone,group B with MФ＋Ti particles,group C with MФ ＋Ti particles ＋ etanercept （10 ng/ml） ,group D with MФ Ti particles ＋ etanercept （100 ng/ml） ,group E with MФ ＋ Ti particles ＋ etanercept （ 1000 ng/ml）. After 18 h, the production of TNF - α IL - 1 and IL - 6 in culture supernatants was detected by ELISA. [ Result] The levels of TNF-α IL - 1 and IL - 6 production were much higher in group B than those in group A, D, E （P 〈0.001 ）. The levels of TNF-α IL- 1 and IL- 6 production were much lower in group E than those in groupB, C （P 〈0.001 ）. There were no significant difference in group E, D（P 〉0.05）. [ Conclusion] Is shows the Ti particles could stimulate MФ to excrete profuse TNF-A IL-1 and IL-6 production, etanercept can significantly inhibited the production of TNF-α IL-1 and IL-6 secreted by Ti particles induced macrophages in a dose-dependent manner and hope to be a therapeutic candidate for the prevention of aseptic loosening.