辛伐他汀对钛颗粒刺激人单核细胞形成破骨细胞的影响

目的研究体外辛伐他汀对钛颗粒刺激单核细胞形成破骨细胞的影响，探讨辛伐他汀防治人工关节无菌性松动的可能性。方法体外分离培养人外周血单个核细胞并分成5组，A组为钛颗粒刺激组（单核细胞和磨屑混合培养），B组为10^-5mol／L辛伐他汀组（单核细胞、磨屑混合培养＋10^-5mol／L辛伐他汀），C组为10^-6mol／L辛伐他汀组（单核细胞、磨屑混合培养＋10^-6mol／L辛伐他汀），D组为10^-7mol／L辛伐他汀组（单核细胞、磨屑混合培养＋10^-7mol／L辛伐他汀），E组为单核细胞组。各组细胞培养24h后取上清液，用ELISA法检测上清液中肿瘤坏死因子（TNF-α）、单核细胞趋化蛋白-1（MCP-1）的含量。分别培养10d、18d后进行TRAP染色阳性细胞计数，采用扫描电镜检测骨磨片的吸收陷窝，观察钛颗粒对破骨细胞形成的影响。结果磨屑刺激单个核细胞分泌溶骨因子，辛伐他汀抑制磨损颗粒刺激单核／巨噬细胞分泌TNF-α及MCP-1；且破骨细胞数明显减少，骨吸收陷窝数减少，与钛颗粒组刺激组比较，差异均有统计学意义（P〈0．05）。结论辛伐他汀通过抑制TNF-α、MCP-1的释放而有效防止磨屑诱导的骨溶解，有望成为防治人工关节无菌性松动的一种有潜力的药物。

Effect of simvastatin on inhibiting osteoclasts cytomorphosis from PBMC stimulated by Ti particles

Objective To investigate the effect of simvastatin on inhibiting osteoclasts cytomorphosis from PBMC stimulated by Ti particles, and the potential prevention effect on the aseptic loosening of prosthesis. Methods In vitro human peripheral blood mononuclear cells （PBMC） were separated, cultured into five groups, as group A： PBMC and Ti particles, group B： PBMC and Ti particles with 10^-5 mol/L simvastatin, group C： PBMC and Ti particles with 10^-6 mol/L simvastatin, group D： PBMC and Ti particles with 10.7 mol/L simvastatin, group E： PBMC group. The productions of TNF-α and MCP-1 in the suspension of each group were tested by ELISA.Afier 10 and 18 days incubation, osteoclasts were counted by TRAP-positive staining and their functions were assessed by absorption laeuna using scanning electron microscope （SEM） on the slice. Results The productions of TNF-α, MCP-1 from PBMC stimulated by Ti particles were inhibited when simvastatin was used, the numbers of osteoclasts and absorption lacuna in the treatment groups were lesser than in the Ti induced group （P 〈0.05）. Conclusion Simvastatin can inhibit bone absorptive factors expression induced by wear particles. As a result, it may be applied to prevent and treat aseptic loosening of prosthesis.