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| Anti-CDllb单克隆抗体对超高分子聚乙烯磨损颗粒诱导骨溶解作用的研究 |
| Anti-CDllb antibody can inhibit osteolysis induced by UHMWPE particles |
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| DOI：10.3969/j.issn.1006.7108.2017.02.002 |
| 中文关键词: CDllb 骨溶解；颗粒 |
| 英文关键词:CDllb Bone dissolution Particle |
| 基金项目:国家自然科学基金资助项目（81301541) |
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| 中文摘要: |
| 目的 通过建立小鼠颅骨溶解模型，探究anti-CDllb抗体对颗粒诱导骨溶解的作用。方法 取10周龄雌性C57BL/6J小鼠32只，平均分为4组,A(空白对照组），切开颅顶皮肤后即缝合，于术后第二天灌胃生理盐水，并尾静脉注射PBS，B[脾酪氨酸激酶（Spleen tyrosine kinase，Syk)抑制剂组]、C( anti-CDllb单克隆抗体组）和D(颗粒组）组于烦骨骨膜外移植20μg超高分子聚乙烯磨损颗粒后缝合，B组术后第2大起以15 mg/kg灌胃Syk抑制剂，尾静脉注射PBS，C组术后第2天起尾静脉注射 anti-CDllb单克隆抗体，2 g/kg,灌胃生理盐水，D组术后第二天起每日灌胃生理盐水，尾静脉注射PBS。两周后颈椎脱臼法处死小鼠，摘眼球取血测血清肿瘤坏死因子α(tumor necrosis factor-α，TNF-α)值，取颅骨做显微CT重建并测骨体积分数，取颅骨骨膜进行western blot分析。结果 建模小鼠全部存活，空白对照组、anti-CDl lb单克隆抗体组及Syk抑制剂组血清TNF-α值均低于颗粒组（P <0. 05);空白对照组、anti-CDllb单克隆抗体组与Syk抑制剂组骨体积分数均高于颗粒组（P < 0. 05 ) ; Syk抑制剂组及anti-CDllb单克隆抗体组Erk活性、c-fos及NFATcl表达均低于颗粒组而高于空白对照组（P < 0. 05 )。结论 Anti- CDllb单克隆抗体及Syk抑制剂均对颗粒诱导骨溶解具有抑制作用，CDllb分子通过激活Syk通路而发挥促破骨细胞分化作用。 |
| 英文摘要: |
| Objective To investigate the effect of anti-CD11 b monoclonal antibody on bone dissolution model. Methods 32 10- week-old C57BL/6J female mice were divided into 4 groups with 8 in each group. Control group (A) received sham operation, then was given normal saline by gavage and received tail intravenous injection of PBS；Spleen tyrosine kinase(Syk) inhibitor group (B) received 20μg Ultrahigh molecular weight polyethylene(UHMWPE)particles implantation onto the calvariae, then was given p505-15, 15 mg/kg by gavage,and received tail intravenous injection of PBS；Anti-CDllb antibody treatment group (C) received 20μg UHMWPE particles implantation, then received tail intravenous injection of anti-CDllb antibody,2g/kg, and was given normal saline by gavage；Particle group (D) received 20μg UHMWPE particles implantation，then was given normal saline by gavage and received tail intravenous injection of PBS. Two weeks later, the blood was used to measure TNF-α, and mouse calvariae were harvested for digital reconstruction using Micro-CT. The skull periostea were harvested for western blot. Results TNF-α levels of group A、B and C were lower than that of group D( P < 0. 05). Bone volume fraction(BVF) of group A、B and C were higher than that of group D( < 0. 05). Erk activity, c-fos and NFATcl of group B and C were lower than that of group D and higher than that of group A(P <0.05). Conclusion Anti-CDllb monoclonal antibody and Syk inhibitor can inhibit particles induced bone dissolution. CDllb can activate its downstream Syk pathway and promote osteoclast differentiation. |
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