IL-4与骨保护素联合抑制聚乙烯磨损颗粒诱导的溶骨效应  

Interleukin-4 and osteoprotegerin suppress polyethylene wear debris-induced osteolysis in a murine air pouch model

作　　者：汪洋[1,2] 周锐[3] 吴宁宁[2] 牟钰钦[4] 李锐冬[1,2] 邓忠良[1] 

机构地区：[1]重庆医科大学附属二院骨科,重庆400010 [2]重庆医科大学检验系临床检验诊断学教育部重点实验室,重庆400016 [3]第三军医大学大坪医院野战外科研究所创伤实验室／创伤、烧伤与复合伤国家重点实验室,重庆400042 [4]重庆医科大学药学院,重庆400016

出　　处：《南方医科大学学报》2011年第10期1709-1713,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(30772211)~~

摘　　要：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。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（P0.05）.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（P0.05）.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.

关 键 词：骨保护素 白介素-4 人工关节 植骨气囊动物模型 无菌松动 

分 类 号：R687.3[医药卫生—骨科学]