摘要
目的 :检测沙利度胺 (Thalidomide ,Thal)对骨水泥微粒刺激巨噬细胞 (Macrophage ,MФ)分泌肿瘤坏死因子a (TumorNecrosisFactor α ,TNF α)的影响 ,探讨药物防治人工关节无菌性松动的可能性。方法 :运用电镜检测MФ吞噬骨水泥微粒的情况 ,MTT方法检测MФ吞噬骨水泥微粒后自分泌物对其增殖的影响 ,分别运用RT PCR、固定化蛋白质印迹法 (Westernblot)及酶联免疫法 (ELISA)检测Thal对接受骨水泥微粒刺激后MФTNF α分泌水平的影响。结果 :电镜证实MФ具有吞噬骨水泥微粒的能力 ,MTT法证实MФ接受骨水泥微粒刺激后分泌的物质对其自身具有促增殖作用 ,且具有剂量依赖性。RT PCR、Westernblot及ELISA方法证实Thal能够在mRNA转录、蛋白表达、细胞因子分泌等多个水平对TNF α具有抑制作用。结论 :骨水泥微粒可刺激MФ增殖和TNF α分泌 ,而Thal能有效地抑制MФ的这种分泌。Thal有可能对由碎屑微粒诱导并由TNF α介导的骨溶解产生抑制作用。
Objective:To detect the effect of thalidomide on the polymethylmethacrylate(PMMA) particles induced TNF-α production by macrophage and to evaluate the validity of the thalidomide on treatment of aseptic loosening of prosthesis.Method:Electron microscopy was used to observe the particles phagocytosis by macrophages.Cell proliferation under their own secretion associated with PMMA particles was measured with MTT assay.TNF-α mRNA and protein expression from PMMA-stimulated macrophage were measured by RT-PCR,Western blot analysis and ELISA.Result:Electron microscopy showed evidence of particles phagocytosis of macrophages.Cell proliferation was enhanced by self-secretion induced by the particles in a dose-dependent manner.All data of RT-PCR,Western blot and ELISA showed that thalidomide inhibited the particle-induced TNF-α production by macrophages both in mRNA and protein levels.Conclusion:TNF-α is involved critically in osteoclastogenesis and bone resorption during periprosthetic osteolysis in human.Thalidomide could inhibit TNF-α secretion from PMMA-stimulated macrophage and may be useful as therapeutic agents for the treatment of prosthetic loosening.
出处
《中国矫形外科杂志》
CAS
CSCD
2004年第13期1002-1005,共4页
Orthopedic Journal of China
