Anti-CD11b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

发布时间：2019-07-04 08:55

【摘要】：目的通过建立小鼠颅骨溶解模型,探究anti-CD11b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-CD11b单克隆抗体组)和D(颗粒组)组于颅骨骨膜外移植20μg超高分子聚乙烯磨损颗粒后缝合,B组术后第2天起以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-CD11b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-CD11b单克隆抗体组及Syk抑制剂组血清TNF-α值均低于颗粒组(P0.05);空白对照组、anti-CD11b单克隆抗体组与Syk抑制剂组骨体积分数均高于颗粒组(P0.05);Syk抑制剂组及anti-CD11b单克隆抗体组Erk活性、c-fos及NFATc1表达均低于颗粒组而高于空白对照组(P0.05)。结论 AntiCD11b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,CD11b分子通过激活Syk通路而发挥促破骨细胞分化作用。
[Abstract]:Objective to investigate the effect of anti-CD11b antibody on osteolysis induced by granule by establishing mouse skull dissolution model. Methods 32 10-week-old female C57BL/6J mice were divided into 4 groups on average:, A (blank control group). The craniocapical skin was sutured immediately after craniotomy. Normal saline was given intragastrically the second day after operation, and PBS,B (spleen casein kinase (Spleen tyrosine kinase,Syk) inhibitor group (, C (anti-CD11b monoclonal antibody group) and D (granule group) were sutured after transplantation of 20 渭 g ultra-high molecular polyethylene wear particles outside the skull periosteum. Group B was treated with 15 mg/kg Syk inhibitor from the 2nd day after operation, and PBS,C group was injected with anti-CD11b monoclonal antibody, 2 g 路kg ~ (- 1) intravenously from the 2nd day after operation, and group D was treated with normal saline every day from the second day after operation, and PBS. was injected intravenously into the tail vein from the second day after operation. Two weeks later, the mice were killed by cervical dislocated method. The serum tumor necrosis factor 伪 (tumor necrosis factor- 伪 (TNF- 伪) was measured. The skull was reconstructed by microCT and the bone volume fraction was measured. The skull periosteum was taken for western blot analysis. Results all the mice survived. The serum TNF- 伪 values in the blank control group, anti-CD11b monoclonal antibody group and Syk inhibitor group were lower than those in the granule group (P 0.05), and the bone volume fraction in the blank control group, anti-CD11b monoclonal antibody group and Syk inhibitor group were higher than those in the granule group (P 0.05). The activity of Erk, the expression of c-fos and NFATc1 in Syk inhibitor group and anti-CD11b monoclonal antibody group were lower than those in granule group, but higher than those in blank control group (P 0.05). Conclusion both AntiCD11b monoclonal antibody and Syk inhibitor can inhibit osteolysis induced by granule. CD11b molecule can promote osteoclast differentiation by activating Syk pathway.
【作者单位】：第四军医大学附属西京医院骨一科;
【基金】：国家自然科学基金资助项目(81301541)
【分类号】：R681

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