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目的通过比较强直性脊柱炎(AS)病人抗肿瘤坏死因子(TNF)-α单克隆抗体药物(remicade)治疗前后的膝关节滑膜细胞的基因谱变化,找出缓解AS病情相关的主要基质金属蛋白酶(MMP)-3,并探讨MMP-3潜在调控的作用和在AS发病中的作用机制和意义。方法从AS病人在remicade治疗前和治疗3个月后的关节滑膜细胞的基因表达谱(用含1176基因的cDNA微阵列检测)结果中筛选的靶基因即差异表达最显著的MMP-3为特异性刺激因子,用反转录-聚合酶链反应(RT-PCR)方法检测它诱导健康志愿者外周血单个核细胞(PBMC)的炎症相关基因TNF-α、c-jun和c-fos的表达。结果比较AS病人治疗前后的关节滑膜细胞基因差异表达的结果,MMP-3治疗后下调最显著(P=0.0147)。与MMP-3聚类在一起的基因有111个,和MMP-3相关性最强的基因是金属蛋白酶抑制剂前体(TIMP)-1;MMP-3能显著诱导PBMC的TNF-α、c-jun和c-fos的表达。结论在remicade治疗AS过程中,下调MMP-3是最重要的环节之一;通过检测MMP-3在关节滑膜细胞组织中的表达水平可作为AS诊断和病情进展监控的参考指标;MMP-3下调,可能使TNF-TNFR2-JNK-AP-1信息通道的激活状态减弱,从而减少致炎因子的释放,调整异常的基质降解和血管形成等病理因素,缓解AS炎症、减少软骨和骨质破坏的作用。
OBJECTIVE: To compare the genomic changes of synovial cells in synovial cells of patients with ankylosing spondylitis (AS) before and after treatment with anti-tumor necrosis factor (TNF) -α monoclonal antibody (remicade) to find out the main matrix metal Protease (MMP) -3, and to explore the underlying regulation of MMP-3 and its role in the pathogenesis and significance of AS. Methods The most significantly differentially expressed MMP-3 gene was screened from the gene expression profile of synoviocytes (detected by cDNA microarray containing 1176 gene) of AS patients before and 3 months after remicade treatment Specific stimulating factor was used to detect the expression of TNF-α, c-jun and c-fos in the peripheral blood mononuclear cells (PBMCs) of healthy volunteers by reverse transcription-polymerase chain reaction expression. Results The results of differential gene expression of synovial cells in patients with AS before and after treatment showed that MMP-3 had the most significant decrease after treatment (P = 0.0147). There are 111 genes clustered together with MMP-3, and the most relevant gene of MMP-3 is TIMP-1. MMP-3 can significantly induce TNF-α, c -jun and c-fos expression. Conclusion The down-regulation of MMP-3 is one of the most important steps in the treatment of AS with remicade. The expression of MMP-3 in synovial tissue can be used as a reference for the diagnosis and progression of AS. MMP-3 Down-regulation may reduce the activation state of TNF-TNFR2-JNK-AP-1 signaling pathway, thereby reducing the release of inflammatory cytokines, regulating abnormal matrix degradation and angiogenesis and other pathological factors, relieve AS inflammation and reduce cartilage and bone destruction Role.