红霉素对人工关节磨屑诱导人单核细胞NF-κB的活化及P65mRNA表达的影响

Effects of erythromycin on NF-κB activity and expression of p65 mRNA in human monocytes induced by UHMWPE debris in vitro

目的探讨红霉素(EM)防治人工关节松动的可能性。方法采集30例人体外周血,分离单核细胞(MOs),实验分6组,每组n=30,A组(对照组):仅MOs;B组:MOs+超高分子聚乙烯微粒(UHMWPE);C组:MOs+UHMWPE+帕米磷酸钠;D组:MOs+UHMWPE+EM(5μg/ml);E组:MOs+UHMWPE+EM(10μg/ml);F组:MOs+UHMWPE+EM(25μg/ml),培养48h后,分别采用反转录-聚合酶链反应(RT-PCR)、免疫印迹法,检测在帕米磷酸钠和不同剂量EM作用下高分子聚乙烯微粒(UHMWPE)诱导MOsp65mRNA表达水平及核蛋白p65含量的变化。结果A、C、D、E、F组的p65mRNA表达水平和核蛋白p65含量均低于B组(P<0.05)。结论EM能有效地抑制由于UHMWPE刺激MOs所致的NF-κB的活化和高表达,能防治人工关节置换术后由微粒诱导的炎症性因子引发的骨溶解。

Objective To explore the effects of erythromyein （EM） on aseptic loosening of prothesis. Methods From 30 healthy human donors, blood samples were taken, which Monocytes （MOs） were isolated and then divided into six groups. Group A was treated with MOs alone, group B with MOs ＋ ultrahigh molecular weight polylethylene （UHMWPE） debris, group C with MOs ＋ UHMWPE ＋ pamidronate （10 μg/ ml）, group D with MOs ＋ UHMWPE ＋ EM （5 μg/ ml）, group E with MOs ＋ UHMWPE ＋ ME（10 μg/ ml）, and group F with MOs ＋ UHMWPE ＋ EM（25 μg/ ml） . They were co-cultured for 48 hours, then the levels of p65 in nucleus and the expression of p65 in MOs was determined. Results The levels of p65 in nucleus and expression of p65 were much higher in group B than those in group A, C, D, E and F （P 〈 0.05）. Conclusions EM inhibits effectively UHMWPE stimulated NF -κB active and expression of p65 in MOs and appears to be a potential therapeutic candidate for the treatment and prevention of aseptic loosening.