雷尼酸锶对钛颗粒诱导炎性骨溶解的抑制作用

目的观察雷尼酸锶（strontium ranelate,SR）对磨损颗粒诱导炎性骨溶解的影响。方法 30只雄性C57BL/J6小鼠,随机分为空白组、对照组和药物组,每组10只。采用钛（Ti）颗粒诱导的小鼠颅骨溶解模型,药物组建模当日经灌胃予SR600mg/（kg·d）],空白组和对照组不予处理;持续至建模后10d,处死取材。HE染色观察颅骨溶解程度及骨膜厚度;抗酒石酸酸性磷酸酶（tartrate resistant acid phosphatase,TRAP）染色检测成熟破骨细胞;酶联免疫吸附试验（ELISA）检测肿瘤坏死因子（TNF-α）、白细胞介素（IL）-1β和IL-6表达水平。结果HE染色结果,对照组骨膜明显增厚,颅骨溶解区域广;图像分析软件测量结果,对照组骨膜厚度（0.27±0.04）mm,骨溶解率为0.47±0.11,与药物组（0.11±0.02）mm,0.18±0.05]比较,差异有统计学意义（P〈0.05）;TRAP染色结果,对照组颅骨大片紫红色区域,SR治疗后明显减少;ELISA检测结果,SR加入后,TNF-α、IL-1β和IL-6的表达量分别为（145.6±14.2）ng/L、（130.2±8.2）ng/L和（137.6±8.2）μg/L],与对照组（210.2±8.9）ng/L、（159.6±9.7）ng/L、（170.8±9.5）μg/L]比较,差异有统计学意义（P〈0.05）。结论 SR能够减轻Ti颗粒引起的炎症反应、减少炎症因子分泌,抑制骨溶解。

Inhibitory effects of strontium ranelate on titanium particle-induced inflammatory osteolysis

Objective To observe the effect of strontium ranelate（SR）on titanium（Ti）particles-induced inflammatory osteolysis through restraining osteoclastogenesis in a murine osteolysis model.Methods Thirty male C57BL/J6mice,8-10weeks old,were enrolled in the study.All experimental animals were randomly divided into three groups：blank group,Ti group,SR group.SR 600mg/（kg·d）]was administrated to mice when the Ti particles were implanted and maintained until the mice were sacrificed.The calvaria were collected 10days after Ti implantation for histological and molecular analyses.HE staining was used to count the bone resorption area and the periosteum thickness of calvaria by using computerized image analysis system.Tartrate-resistant acid-phosphatase（TRAP）staining was done to determine the number of osteoclast-like cells.The levels of tumor necrosis factor-α（TNF-α）,interleukin-1β（IL-1β）and IL-6 were examined by enzyme linked immunoabsorbent assay（ELISA）.Results The quantitative image analysis of histological sections revealed that the bone resorption area and the periosteum thickness of calvaria were remarkably different among the three groups（P0.05）.TRAP staining showed that SR could significantly decrease the number of TRAP positive cells in calvaria as compared with Ti group（P0.05）.The results of ELISA suggested that SR could significantly reduce the protein level of TNF-α,IL-1βand IL-6induced by Ti particles in a murine osteolysis model.Conclusion This study provides evidence that SR can markedly inhibit Ti-particle-induced inflammatory osteolysis,and could be developed as a potential compound for the prevention and treatment of osteolysis and subsequent aseptic loosening after total joint replacement.