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基质金属蛋白酶(MMP)-9 及其特异性抑制剂 TIMP-1 在膝关节感染性和非感染性关节炎中的表达水平。

Expression levels of matrix metalloproteinase (MMP)-9 and its specific inhibitor TIMP-1, in septic and aseptic arthritis of the knee.

机构信息

Department of Medicine, University of Ioannina, Ioannina, Greece.

出版信息

Knee Surg Sports Traumatol Arthrosc. 2012 Jun;20(6):1159-67. doi: 10.1007/s00167-011-1676-9. Epub 2011 Sep 24.

DOI:10.1007/s00167-011-1676-9
PMID:21946941
Abstract

PURPOSE

In cases of septic knee arthritis, there is excess of matrix metalloproteinases (MMPs) over tissue inhibitors of metalloproteinases (TIMPs), due to enhanced expression and activation that are induced by bacteria in comparison with rheumatic or degenerative arthritis. The aim of this study was to explore the expression levels of synovial gelatinase MMP-9 and its specific inhibitor TIMP-1 in septic and aseptic arthritis and their potential use as additional aids to clinical investigation.

METHODS

Gelatin zymography and western blot analysis were applied in effusions from knees of the patients with septic (SA-10 patients), rheumatic (RA-10 patients) and osteoarthritis (OA-10 patients).

RESULTS

Zymographic analysis revealed that all samples contained latent MMP-2 activity, albeit activated MMP-2 appeared in more of the septic than aseptic effusions. MMP-9 was not detected in osteoarthritic synovial fluid samples. Only trace amounts of MMP-9 activity were detected in 4 of 10 patients with RA, whereas higher MMP-9 levels were evident in all samples from SA (P = 0.0241). In immunoblotting assays, samples from SA showed significantly higher levels of MMP-9 compared with samples from RA (P = 0.0052), confirming zymographic results. Although no significant difference in TIMP-1 levels was observed, the estimated MMP-9/TIMP-1 ratio of septic effusions was significantly higher compared with aseptic ones (P = 0.0029).

CONCLUSIONS

The data presented suggest enhanced expression and activation of MMP-9 in septic native knee arthritis compared with aseptic. The presence of high levels of MMP-9 with concomitantly increased MMP-9/TIMP-1 ratio and activated gelatinases in effusions, independent of neutrophilic counts, may be indicative for infection.

摘要

目的

在感染性膝关节炎中,由于细菌诱导的基质金属蛋白酶(MMPs)表达和激活增强,MMPs 相对于风湿性或退行性关节炎的组织抑制剂(TIMPs)过量。本研究旨在探讨滑液明胶酶 MMP-9 及其特异性抑制剂 TIMP-1 在感染性和无菌性关节炎中的表达水平,并将其作为临床研究的辅助手段。

方法

采用凝胶电泳酶谱分析和 Western blot 分析方法检测 10 例感染性关节炎(SA)、10 例风湿性关节炎(RA)和 10 例骨关节炎(OA)患者膝关节积液中的 MMP-9 和 TIMP-1 表达。

结果

酶谱分析显示,所有样本均含有潜伏型 MMP-2 活性,但在感染性关节炎患者的关节液中,激活型 MMP-2 更为常见。OA 患者的滑液中未检测到 MMP-9。10 例 RA 患者中有 4 例仅检测到痕量 MMP-9 活性,而所有 SA 患者的关节液中 MMP-9 水平均明显升高(P = 0.0241)。在免疫印迹分析中,SA 组样本的 MMP-9 水平明显高于 RA 组(P = 0.0052),与酶谱分析结果一致。TIMP-1 水平无明显差异,但感染性关节炎关节液的 MMP-9/TIMP-1 比值明显高于无菌性关节炎(P = 0.0029)。

结论

与无菌性关节炎相比,感染性膝关节原发性关节炎中 MMP-9 的表达和激活增强。关节液中 MMP-9 水平升高,同时 MMP-9/TIMP-1 比值升高,明胶酶激活,与中性粒细胞计数无关,可能提示感染。

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