细胞外基质金属蛋白酶诱导因子及基质金属蛋白酶9在镁硅玉人工关节假体无菌性松动中的作用

INFLUENCE AND ROLE OF EXPRESSION OF EXTRACELLULAR MATRIX METALLOPROTEINASE INDUCER AND MATRIX METALLOPROTEINASE 9 IN ASEPTIC LOOSENING OF PROSTHESIS

目的观察细胞外基质金属蛋白酶诱导因子(extracellular matrix metalloproteinase inducer,EMMPRIN)及基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)在镁硅玉人工关节假体周围各区的表达和分布变化,探讨髋臼侧及股骨侧各区EMMPRIN和MMP-9表达变化与骨溶解之间的关系。方法取2010年2月-2012年1月8例8髋采用镁硅玉人工关节置换后,因假体无菌性松动行髋关节翻修术中取出的滑膜组织作为实验标本,术中按Delee-Charnley髋臼分区法和Gruen股骨分区法取出假体周围各区界膜组织,并结合术前X线片和术中观察,将其分为溶骨区组和非溶骨区组;另取同期8例8髋行关节置换的骨关节炎患者滑膜组织作为对照组。采用组织学观察、免疫组织化学染色法及RT-PCR检测EMMPRIN和MMP-9及其mRNA表达,比较分析各组、各区表达差异。结果组织学观察发现溶骨区组界膜组织中可见大量巨噬细胞,多核巨细胞聚集增生;非溶骨区组以纤维细胞为主。各组均可见EMMPRIN和MMP-9阳性细胞及基因表达;其中假体周围溶骨区组EMMPRIN、MMP-9阳性细胞率及基因表达均明显高于非溶骨区组和对照组(P<0.05),非溶骨区组和对照组比较差异无统计学意义(P>0.05)。翻修患者髋臼侧Ⅲ区EMMPRIN阳性细胞率高于Ⅰ、Ⅱ区(P<0.05),I、Ⅱ区比较差异无统计学意义(P>0.05);Ⅰ、Ⅲ区MMP-9阳性细胞率显著高于Ⅱ区(P<0.05),Ⅰ、Ⅲ区比较差异无统计学意义(P>0.05)。股骨侧各区EMMPRIN阳性细胞率由高到低依次为1、7、4、2、3、5、6区,1、7、4区明显高于2、3、5、6区(P<0.05),1、7、4区间及2、3、5、6区间比较差异无统计学意义(P>0.05);MMP-9阳性细胞率从高到低依次为l、7、4、2、3、6、5区,1、7区明显高于4、2、3、6、5区(P<0.05),4、2区高于3、6、5区(P<0.05),1区与7区间、4区与2区间以及3、5、6区间差异均无统计学意义(P>0.05)。结论假体周围EMMPRIN和MMP-9的表达具有一定一致性,其异常表达可能是磨损颗粒造成假体周围骨溶解发生的关键环节之一。

ObjectiveTo observe the expressions of extracellular matrix metalloproteinase inducer （EMMPRIN） and matrix metalloproteinase 9 （MMP-9） around the prosthesis, and to study the relationship between the expressions of EMMPRIN and MMP-9 and osteolysis around prosthesis. MethodsInterface tissues were obtained at three Delee-Charnley acetabular sections and seven Gruen femur sections from 8 cases （8 hips） undergoing revision after total hip arthroplasty between February 2010 and January 2012, and were divided into osteolysis group and non-osteolysis group based on preoperative X-ray film and intraoperative observation; the tissues from another 8 patients with osteoarthritis undergoing total hip arthroplasty as the control group. The immunohistochemical staining and RT-PCR assays were used to determine the expressions of EMMPRIN and MMP- 9. The correlation between the positive cells and the severity of osteolysis were analyzed and compared. ResultsHistological examination showed that many macrophages, multinucleated giant cells assembled in the membrane of osteolysis zone, but many fibroblasts and synovial cells in non-osteolysis zones. EMMPRIN and MMP- 9 positive cells and gene expressions were observed in every group. The percentage of positive cells and gene expression of EMMPRIN and MMP-9 in osteolysis group were significantly higher than those in non-osteolysis and control groups （P 〈 0.05）, but no significant difference was found between non-osteolysis group and control group （P 〉 0.05）. The percentage of positive cells of EMMPRIN in zone III of acetabular was higher than that in zone I and zone II of revision hip （P 〈 0.05）, but no significant difference between zone I and zone II （P 〉 0.05）. The percentage of positive cells of MMP-9 in zone I and zone III was significantly higher than that in zone II of revision hip （P 〈 0.05）, but no significant difference between zone I and zone III （P 〉 0.05）. The expression of EMMPRIN from high to low in order was zones 1, 7, 4, 2, 3, 5, and 6 at femur; the values of zones 1, 7, and 4 were significantly higher than those of zones 2, 3, 5, and 6 （P 〈 0.05）, but no significant difference among zones 1, 7, and 4, and among zones 2, 3, 5, and 6 （P 〉 0.05）. The expression of MMP-9 from high to low in order was zones 1, 7, 4, 2, 3, 6, and 5 at femur; the values of zones 1 and 7 were significantly higher than those of zones 4, 2, 3, 6, and 5 （P 〈 0.05）, and the values of zones 4 and 2 were significantly higher than those of zones 3, 6, and 5 （P 〈 0.05）, but no significant difference between zone 1 and zone 7, between zone 4 and zone 2, and among zones 3, 5, and 6 （P 〉 0.05）. ConclusionThe expressions of EMMPRIN and MMP-9 have certain coherence. The over-expressions of EMMPRIN and MMP-9 may be one of the key points of inhibiting bone reconstruction and bone resorption at bone-implant interface under the stimulation of wear debris．