SCID小鼠单次唑来磷酸头皮下注射抑制人假体周围骨溶解

Inhibitory effect of zoledronic acid on osteolysis induced by human periprosthetic tissue:an animal study

[目的]评价唑来磷酸在新型动物模型中对人关节假体周围界膜组织诱导的骨溶解的抑制效应。[方法]将髋关节翻修病人体内获得的界膜组织移植到SCIDbeige小鼠颅骨上。术后2d将唑来磷酸直接注射至小鼠头皮下,并在术后2、4周处死动物取出带移植组织的颅骨进一步检测。[结果]移植组织在动物体内存活至少4周,HE染色可见界膜组织引起大量的骨胶原纤维碎裂溶解。界膜组织中TNF-α、IL-6、RANKL和CPK的基因表达和蛋白水平均显著高于对照。单次局部注射唑来磷酸显著降低RANKL和CPK的表达但未影响TNF-α和IL-6的水平。[结论]单次局部注射唑来磷酸可有效抑制人界膜组织诱导的骨溶解,且效应持续。该新型动物模型模拟临床程度高,可作为评价假体周围骨溶解药物抑制效应的平台。

[Objective]To investigate the inhibitory effect of zoledronic acid（ZA） on osteolysis induced by human periprosthetic tissue in a novel animal model.[Method]Human periprosthetic tissue that was harvested from a patient receiving total hip revision was grafted on the calvaria bone of SCID beige mice. ZA was injected directly beneath the scalp of mice once,2 days post surgery. The mice were sacrificed 2 or 4 weeks after transplantation and the calvaria with grafted human tissue was collected for further detection.[Result]The grafted tissues were found survive for at least 4 weeks in the animals. Bone collagen collapse of the calvaria caused by periprosthetic tissue was demonstrated by HE staining. Significantly higher level of TNF-α,IL-6,RANKL and CPK both in gene expression and protein release were detected in PT grafted group,as compared with the control. Once administration of ZA remarkably reduced the expression of RANKL and CPK in both gene and protein level without affecting TNF-α and IL-6.[Conclusion]Once and local injection of ZA effectively inhibits the osteolysis induced by human periprosthetic tissue with a long lasting effect. The novel animal model could serve for evaluating the pharmaceutical effect on periprosthetic osteolysis.