雷公藤多甙对强直性脊柱炎患者血清MMP-3、IL-6水平的影响
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摘要
目的：
通过检测雷公藤多甙(GTW)治疗AS患者不同时间点血清中基质金属蛋白酶(matrix metalloproteinase, MMP)-3和白介素-6 (interleukin, IL-6)的表达水平变化,分析其与AS疾病活动的相关性,并探讨GTW治疗AS发挥作用的可能机制。
方法：
1.分别在治疗0、2、6、12周时留取本研究临床研究中22例AS患者空腹血清,应用酶联免疫吸附试验(ELISA)测定MMP-3和IL-6水平。
2.分析血清MMP-3、IL-6表达水平与AS疾病活动指标如强直性脊柱炎疾病活动指数(BASDAI)、强直性脊柱炎功能指数(BASFI)、血沉(ESR)和C反应蛋白(CRP)等之间的相关性。
结果：
ELISA方法检测22例AS患者GTW治疗不同点血清MMP-3、IL-6水平,结果显示：
1.12周时,血清MMP-3水平与O周有显著下降(P<0.01),0、12周时与BASDAI、BASFI、ESR (P<0.05)相关,而与病人总体评估(PGA)、夜间痛、脊柱痛、脊柱炎症、强直性脊柱炎测量指数(BASMI)、肌腱端指数(EI)、关节肿胀数和扩胸度无相关性。
2.6周、12周时,血清IL-6水平与0周有显著下降(P<0.01),而二者间无统计学意义(P>0.05)；0周、6周时IL-6水平与脊柱炎症及ESR显著相关(P<0.01),12周时IL-6水平与BASDAI显著相关(P<0.01)。
结论：
1.GTW能降低患者血清MMP-3和IL-6水平,这可能是其发挥临床疗效的机制。
2.血清MMP-3和IL-6可作为预测GTW治疗AS疾病进展及病情活动的潜在生物学标志物。
Objective
To investigate the changes of serum matrix metalloproteinase(MMP)-3 and interleukin(IL-6 level in different times treating ankylosing spondylitis(AS) with multi-glycosideofTripterygium wilfordii Hook. f. (GTW) and to explore their meaning in diseases activity and possible link to therapy response.
Methods
Peripheral bloods of 0,2,6,12 weeks were collected from 22 patients with AS who received GTW. Serum MMP-3 level and IL-6 level were measured by sandwich enzyme-linked immunosorbent assay(ELISA).
Further respectively analyze the relationship among MMP-3, IL-6, ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis functional index (BASFI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and so on.
Results
1. The MMP-3 level decreased statistically after 12 weeks GTW treatment with 0 week(P<0.01). The level of MMP-3 showed correlation with BASDAI, BASFI, ESR at 0 week or 12 weeks and no correlation with other indexes.
2. The IL-6 level decreased statistically at 6 weeks or 12 weeks after GTW treatment compared with 0 week(P<0.01), but no variability between them. The level of IL-6 showed correlation with spinal inflammation and ESR at 0 week or 12 weeks and with BASDAI at 12 weeks, and no correlation with other indexes.
Conclusion
1. The therapy of GTW can effectively cut down the serum MMP-3 level and IL-6 level in AS patients. This is likely to be a relevant mechanism for the clinical efficacy of GTW therapy.
2. Serum MMP-3 and IL-6 level could be used as potential biomarkers to evaluate disease progression and disease activity.in AS patients of GTW treatment..
通过检测雷公藤多甙(GTW)治疗AS患者不同时间点血清中基质金属蛋白酶(matrix metalloproteinase, MMP)-3和白介素-6 (interleukin, IL-6)的表达水平变化,分析其与AS疾病活动的相关性,并探讨GTW治疗AS发挥作用的可能机制。
方法：
1.分别在治疗0、2、6、12周时留取本研究临床研究中22例AS患者空腹血清,应用酶联免疫吸附试验(ELISA)测定MMP-3和IL-6水平。
2.分析血清MMP-3、IL-6表达水平与AS疾病活动指标如强直性脊柱炎疾病活动指数(BASDAI)、强直性脊柱炎功能指数(BASFI)、血沉(ESR)和C反应蛋白(CRP)等之间的相关性。
结果：
ELISA方法检测22例AS患者GTW治疗不同点血清MMP-3、IL-6水平,结果显示：
1.12周时,血清MMP-3水平与O周有显著下降(P<0.01),0、12周时与BASDAI、BASFI、ESR (P<0.05)相关,而与病人总体评估(PGA)、夜间痛、脊柱痛、脊柱炎症、强直性脊柱炎测量指数(BASMI)、肌腱端指数(EI)、关节肿胀数和扩胸度无相关性。
2.6周、12周时,血清IL-6水平与0周有显著下降(P<0.01),而二者间无统计学意义(P>0.05)；0周、6周时IL-6水平与脊柱炎症及ESR显著相关(P<0.01),12周时IL-6水平与BASDAI显著相关(P<0.01)。
结论：
1.GTW能降低患者血清MMP-3和IL-6水平,这可能是其发挥临床疗效的机制。
2.血清MMP-3和IL-6可作为预测GTW治疗AS疾病进展及病情活动的潜在生物学标志物。
Objective
To investigate the changes of serum matrix metalloproteinase(MMP)-3 and interleukin(IL-6 level in different times treating ankylosing spondylitis(AS) with multi-glycosideofTripterygium wilfordii Hook. f. (GTW) and to explore their meaning in diseases activity and possible link to therapy response.
Methods
Peripheral bloods of 0,2,6,12 weeks were collected from 22 patients with AS who received GTW. Serum MMP-3 level and IL-6 level were measured by sandwich enzyme-linked immunosorbent assay(ELISA).
Further respectively analyze the relationship among MMP-3, IL-6, ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis functional index (BASFI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and so on.
Results
1. The MMP-3 level decreased statistically after 12 weeks GTW treatment with 0 week(P<0.01). The level of MMP-3 showed correlation with BASDAI, BASFI, ESR at 0 week or 12 weeks and no correlation with other indexes.
2. The IL-6 level decreased statistically at 6 weeks or 12 weeks after GTW treatment compared with 0 week(P<0.01), but no variability between them. The level of IL-6 showed correlation with spinal inflammation and ESR at 0 week or 12 weeks and with BASDAI at 12 weeks, and no correlation with other indexes.
Conclusion
1. The therapy of GTW can effectively cut down the serum MMP-3 level and IL-6 level in AS patients. This is likely to be a relevant mechanism for the clinical efficacy of GTW therapy.
2. Serum MMP-3 and IL-6 level could be used as potential biomarkers to evaluate disease progression and disease activity.in AS patients of GTW treatment..
引文
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[11]Tao QS, Ren JA, Li JS. riptolide suppresses IL-1 beta-induced chemokine and stromelysin-1 gene expression in human colonic subepithelial myofibroblasts.Acta Phanacol Sin.2007 Jan;28(1):81-8.
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[2]Boonen A, Chorus A, Miedema H, et al. Employment, work disability, and work days lost in patients with ankylosing spondylitis:a cross sectional study of Dutch patients. Ann Rheum Dis 2001;60:353-8.
[3]Chen J, Liu C:Is sulfasalazine effective in ankylosing spondylitis? A systematic review of randomized controlled trials. J Rheumatol 2006; 33:722.
[4]张莉芸,黄烽.生物制剂治疗强直性脊柱炎研究进展.中华风湿病学杂志,2005,9：112-115.
[5]van der, Heijde D, Landewe, R, Einstein, S, et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 2008; 58:1324.
[6]Lipsky PE, Tao X-L:A potential new treatment for Rheumatoid Arthritis:Thunder God Vine. Semiars in Arth Rheum 1997,26:713-723.
[7]Tao X, Sun Y, Dong Y, et al.:A prospective, controlled double-blind, cross-over study of Tripterygium wilfordii Hook F in treatment of rheumatoid arthritis. Chin Med J 1989, 102:327-332. Abstract publihsed in Arth & Rheum 1987.
[8]Tao X, Younger J,Fan FZ et al. Benefit of an extract of Tripterygium wilfordii Hook F in patients with rheumatoid arthritis:a double-blind, placebo-controlled study.Arth & Rheum 2002,46:1735-1743.
[9]Liacini A, Sylvester J, Zafarullah M. Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes. Biochem Biophys Res Commun 2005 Feb4;327(1):320-7.
[10]Sylvester J, Liacini A, Li WQ et al. Tripterygium wilfordii Hook F extract suppresses proinflammatory cytokine-induced expression of matrix metalloproteinase genes in articular chondrocytes by inhibiting activating protein-1 and nuclear factor-kappaB. Mol Pharmacol.2001 May;59(5):1196-205.
[11]Tao QS, Ren JA, Li JS. riptolide suppresses IL-1 beta-induced chemokine and stromelysin-1 gene expression in human colonic subepithelial myofibroblasts.Acta Phanacol Sin.2007 Jan;28(1):81-8.
[12]Cui D, Hoshii Y, Kawano H et al. Experimental AA amyloidosis in mice is inhibited by treatment with triptolide, a purified traditional Chinese medicine., Int Immunopharmacol. 2007 Sep;7(9):1232-40. Epub 2007 Jun 8.
[13]Hu GH, Yi ZW, Wang JH, Yao JC. Effect of triptergium wilfordii polyglycosidium on content of Thl and Th2 in child recurrent nephrotic syndrome. Zhongguo Zhong Yao Za Zhi.2008 Feb;33(4):441-3.
[14]Guo Y, Yu M, Jiang Y, Song Q, Dong Y. Effect of Tripterygium Wilfordii Hook T4 monomer on proliferation and interleukin-6 production of synovial fibroblasts of patien-ts with rheumatoid arthritis Zhongguo Yi Xue Ke Xue Yuan Xue Bao.2000 Apr;22(2): 190-2.
[15]Gratacos J, Collado A, Pons F et al. Significant loss of bone mass in patients with early, active ankylosing spondylitis:a followup study. Arthritis Rheum 1999;42:2319-2324.
[16]Fraser A, Fearon U, Reece R, Emery P, Veale DJ. Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis. Arthritis Rheum,2001,44:2024～2028.
[17]Nagashima M, Wauke K, Hirano D et al. Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial growth factor and basic fibroblast growth factor in cultured synoviocytes and patients with rheumatoid arthritis. Rheumatology,2000,39: 1255～1262.
[18]Sone H, Sakauchi M, Takahashi A et al. Elevated levels of vascular endothelial growth factor in the sera of patients with rheumatoid arthritis correlation with disease activity. Life Sci,2001,69:1861～1869.
[19]Nagase H, Woessner JF Jr. Matrix metalloproteinases. J Biol Chem 1999; 274:21491-4.
[20]Ishiguro N, Ito T, Miyazaki K et al. Matrix metalloproteinases, tissue inhibitors of metalloproteinases, and glycosaminoglycans in synovial fluid from patients with rheumatoid arthritis. J Rheumatol 1999; 26:34-40.
[21]Ishiguro N, Ito T, Obata K et al. Determination of stromelysin-1,72 and 92 kDa type IV collagenase, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in synovial fluid and serum from patients with rheumatoid arthritis. J Rheumatol 1996;23:1599-1604.
[22]Carotti M, Salaffi F, Manganelli P et al. Doppler sonography in the assessment of synovial tissue of the knee joint in rheumatoid arthritis:a preliminary experience. Ann Rheum Dis, 2002,61:877～882.
[23]Dougados M, van der, Heijde D. Ankylosing spondylitis:how should the disease be assessed? Best Pract Res Clin Rheumatol,2002,16:605～618.
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