分析人工髋关节置换术后骨溶解及假体松动的分子生物学机制

分析人工髋关节置换术后骨溶解及假体松动的分子生物学机制【摘要】 目的 探讨人工髋关节假体分离出的颗粒碎片刺激巨噬细胞而释放的肿瘤坏死因子(TNF-α)在人工髋关节术后引起骨溶解的作用机理。方法 采纳钛颗粒刺激巨噬细胞而释放 TNF-α 模型及酶联免疫吸附剂测定、蛋白质印迹、凝胶迁移率实验方法来讨论其生物分子学机制。结果 鼠类巨噬细胞受钛颗粒刺激而释放 TNF-α，而 JNK 抑制剂 SP600125 和 NF-кB 抑制剂 MG132 大大抑制了钛颗粒诱导的 TNF-α 释放，但 p38 抑制剂无此作用，甚至，钛颗粒诱导巨噬细胞而激活 AP-1 和 NF-кB。结论 钛颗粒诱导的 TNF-α 释放与JNK/AP-1 及 NF-кB 通路有关。【关键词】 人工髋关节置换术 钛颗粒 骨溶解 肿瘤坏死因子 【Abstract】 Objective To study the mechanism of osteolysis after total hip replacement by tumor necrosis factor-α (TNF-α) release in macrophages stimulated with particulate debris from prosthesis. Methods A model of TNF-α release by stimulating macrophages with titanium particles was made and study the mechanism of TNF-α release by Elisa/West blot/EMSA. Results TNF-α was released in murine macrophage stimulated by titanium (Ti) particles and specific inhibitors of JNK (SP600125) and NF-κB (MG132), but not p38 (SB203580) dramatically inhibited Ti-stimulated TNF-α release. Moreover,transcriptional activation of AP-1 and NF-κB was also induced by Ti particles. Conclusion These results demonstrate that Ti particle-induced TNF-α release is mediated through JNK/AP-1 as well as NF-κB pathways. 【Key words】 THR; Ti particles; osteolysis; TNF 人工髋关节置换术后假体周围的骨溶解及随后而来的假体疏松是置换术失败的常见原因。由于假体长时间磨损与腐蚀生成的颗粒碎片导致假体周围形成假膜，这些假膜由肉芽肿形成，它包括巨噬细胞、纤维母细胞、巨细胞及破骨细胞［1，2］。假体周围膜组织的这些细胞受这些碎片颗粒而产生有关骨溶解及假体松动的炎症因子如 TNF-α、白细胞介素-1β、白细胞介素-6、白细胞介素-8、白细胞介素-11 及转化生长因子-β...