Objective To test the effect of recombinant interleukin-4 (IL-4) and recombinant osteoprotegerin (OPG) in suppressing bone resorption induced by polyethylene wear particles. Methods A cranial bone allograft was introduced into the air pouches induced on the back of BALB/c mice, followed by injection of 1 ml suspension of polyethylene particles into the pouches. The mouse models were then divided into 3 groups to receive injections of saline (control), IL-4 alone, or IL-4 and OPG into the pouches. The tissues were harvested 21 days after bone implantation for molecular and histological analyses. Results Polyethylene wear particles-stimulated inflammatory responses (increased cellular infiltration and IL-1 and TNF production) were markedly reduced by IL-4 treatment either alone or combined with OPG (P<0.05). Polyethylene particles significantly increased tartrate-resistant acid phosphatase (TRAP) staining and bone absorption of the implanted bone graft, and IL-4 treatment, either alone or combined with OPG, obviously reduced the osteolysis induced by polyethylene particles (P<0.05). Conclusion IL-4 offers protection against polyethylene wear debris-induced inflammation and bone resorption in this mouse model. IL-4 combined with OPG can be a feasible and effective therapeutic approach to the treatment and prevention of polyethylene wear debris-associated osteolysis and aseptic loosening of the prosthetic components.%目的 运用小鼠植骨气囊模型,研究白介素-4(IL-4)与骨保护素(OPG)联合减少骨破坏吸收防治人工关节松动的效应.方法 在小鼠背部注入空气形成气囊,取同源小鼠的颅骨植入气囊内.将已制成的气囊模型小鼠分成3组:对照组(气囊注入聚乙烯颗粒及生理盐水)；IL-4组(气囊内注入聚乙烯颗粒及IL-4)；联合组(气囊内注入聚乙烯颗粒、IL-4及OPG),3周后取囊壁和植入颅骨组织进行HE染色检测炎症反应情况及炎症细胞渗出量；取组织匀浆液应用ELISA方法检测炎性细胞因子(IL-1、TNF)浓度；抗酒石酸酸性磷酸酶染色观察破骨细胞的分化成熟情况；应用扫描电镜检测骨片吸收情况.结果 (1)HE染色检测炎症细胞渗出量IL-4组、联合组明显少于对照组(P＜0.05).(2)ELISA法检测炎性细胞因子(IL-1、TNF)浓度IL-4组与联合组均明显少于对照组(P＜0.05).(3)抗酒石酸酸性磷酸酶染色阳性区域与视野面积的百分比IL-4组与联合组明显少于对照组,且联合组较IL-4组染色面积也有显著减少(P＜0.05).(4)应用扫描电镜检测骨片吸收陷窝面积与视野面积的百分比IL-4组与联合组明显少于对照组；且联合组较IL-4组的骨片吸收面积有显著减少.讨论 证实IL-4不仅能明显减轻炎症情况,并且能明显减少破骨细胞的激活、骨破坏吸收情况,抑制聚乙烯磨损颗粒所致的骨吸收效应.IL-4与OPG联合应用于小鼠植骨气囊模型中,其抑制骨吸收效应更加明显.
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