磨损颗粒刺激巨噬细胞引起人工关节松动的作用机制

The mechanism of artificial joint loosening caused by macrophages challenged with wear debris

目的探讨来源于人外周血的单核/巨噬细胞对直径1μm以下超高分子聚乙烯(UHMWPE)磨损颗粒的反应及其机制。方法从因无菌性人工髋关节松动而需要行翻修手术的患者假体周围组织中提取UHMWPE磨损颗粒。从10名健康志愿者分别抽取50ml外周血,梯度离心获得外周血中的单核/巨噬细胞。将细胞分为6组:A:单核/巨噬细胞+UHMWPE磨损颗粒;B:单核/巨噬细胞+UHMWPE磨损颗粒+100μMRote-none;C:单核/巨噬细胞+UHMWPE磨损颗粒+10μMU0126;D:单核/巨噬细胞+UHMWPE磨损颗粒+10ng/mlCerivastatin;E:单核/巨噬细胞;F:单核/巨噬细胞+脂多糖(LPS)。检测各组细胞的TNFα表达。结果UHMWPE磨损颗粒明显刺激单核/巨噬细胞分泌TNFα。Rotenone、U0126和Cerivastatin均可抑制UHMWPE磨损颗粒刺激单核/巨噬细胞分泌TNFα,且以U0126明显(P<0.01)。结论UHMWPE磨损颗粒刺激单核/巨噬细胞产生TNFα可通过NF-κB和MAPK通路,但以MAPK通路为主。

Objective approach the mechanism and effect of UHMWPE particles （ less than 1 μm） on monocyte/macrophages come from human peripheral blood, Methods Harvested UHMWPE particles taken from the operation of hip revision （mean sizes： 0.71 μm） were coultured with the monocyte/macrophages at particle volume （ μm3 ） to cell number ratios of 10 ： 1. Monocyte/macrophages were separated from the peripheral blood of ten donors by density gradient centrifugation techniques. The cells were divided into 6 groups, Group A ： monocyte/macrophages ＋ UHMWPE particles ; Group B ： monocyte/ macrophages ＋ UHMWPE particles ＋ 100 μM Rotenone; Group C： monocyte/macrophages ＋ UHMWPE particles ＋ 10 μM U0126; Group D- monocyte/Macrophages ＋ UHMWPE particles ＋ 10 ng/ml Cerivastatin; Group E： monocyte/macrophages; Group F： monocyte/macrophages ＋ LPS. TNFα was measured after co-cultured for 3h. Results UHMWPE particles in the cell culture provoked higher secretions of TNFα, while Rotenone, U0126 and Cerivastatin inhibited cells to secret TNFα, especially for U0126 （P 〈0. 01 ）. Conclusions UHMWPE particles stimulated monoeyte/macrophages to secrete TNFα, through both NF-κB and MAPK pathway, but mainly through MAPK pathway.