[1]王欢 王庆甫△ 石鑫超 杨黎黎 赵军 张栋 王伟利 丁昊彬.TLRs与NF-kB在大鼠骨关节炎滑膜中的表达及意义[J].中国中医骨伤科杂志,2016,24(06):4-8.
 WANG Huan WANG Qingfu SHI Xinchao YANG Lili ZHAO Jun ZHANG Dong WANG Weili DING Haobin.Expression and Significance of TLRs and NF-kB in Knee Osteoarhritic Synovial of Rats[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2016,24(06):4-8.
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TLRs与NF-kB在大鼠骨关节炎滑膜中的表达及意义
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《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第24卷
期数:
2016年06期
页码:
4-8
栏目:
实验研究
出版日期:
2016-06-10

文章信息/Info

Title:
Expression and Significance of TLRs and NF-kB in Knee Osteoarhritic Synovial of Rats
文章编号:
1005-0205(2016)06-0004-05
作者:
王欢1 王庆甫2△ 石鑫超1 杨黎黎1 赵军1 张栋1 王伟利1 丁昊彬1
1.北京中医药大学(北京,100029)
2.北京中医药大学第三附属医院
△.通信作者 E-mail:qingpu-wang@sohu.com
Author(s):
WANG Huan1 WANG Qingfu2△ SHI Xinchao1 YANG Lili1 ZHAO Jun1 ZHANG Dong1 WANG Weili1 DING Haobin1
1.Beijing University of Chinese Medicine,Beijing 100029,China;
2.The Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029,China.
关键词:
骨关节炎 Toll样受体2(TLR2) Toll样受体4(TLR4) 核因子-kB(NF-kB) 滑膜
Keywords:
osteoarthritis Toll-like receptor 2(TLR2) Toll-like receptor 4(TLR4) nuclear factor-kB(NF-kB) synovial membrane
分类号:
R-33
文献标志码:
A
摘要:
目的:探讨不同造模时间下大鼠滑膜组织中的Toll样受体(Toll-like Receptors,TLRs)和核因子-kB(NF-kB)在骨关节炎(Osteoarthritis,OA)病程中的内在联系,研究其表达特点及变化规律。方法:将80只Wistar大鼠随机分为5组,每组16只。模型组大鼠利用经典Hulth法建立2,4,6周膝OA动物模型,同样方式切开假手术组皮肤及关节囊进入关节腔,空白对照组不予手术。按期提取滑膜样本,对其进行形态学观察并用实时PCR法检测各组滑膜组织中TLR2,TLR4及NF-kB的表达。结果:重度OA模型中的TLR2表达显著增加(P<0.05); 随着造模时间的延长,TLR4的表达逐渐受到抑制(P<0.05); NF-kB在2,4,6周模型组中均大量表达(P<0.05),且表达量与造模时间成正比。结论:大鼠膝关节OA模型造模成功,OA病程时间与TLR2,TLR4和NF-kB 的表达之间存在显著的相关性,三者是导致OA发生的重要影响因子。
Abstract:
Objective: To investigate internal influence of the expression of Toll-like receptors(TLRs)and nuclear factor-kB(NF-kB)in the synovial tissue of rats at different modeling time points in the process of osteoarthritis(OA), as well as to explore the expression features and the change rules. Methods: All 80 Wistar rats were randomly divided into five groups, 16 rats in each group. Surgery Groups(knee OA model of 2 weeks, 4 weeks, and 6 weeks)were intervened by classical Hulth methods. For the sham operation group was only exposed the knee joint cavity, while no surgery was applied in the blank control group. The samples of knee osteoarhritic synovial tissue were extracted at 2 weeks, 4 weeks and 6 weeks after the surgery respectively. The morphology of synovial tissue was observed, and the expression of TLR2, TLR4, and NF-kB of synovial tissue were detected by Real-time PCR methods. Results: The expression of TLR2 in the severe OA group were increased significantly(P<0.05). The expression of TLR4 was inhibited gradually with the extension of modeling time(P<0.05). The expression of NF-kB was abundantly expressed in the mild, moderate, and severe grade model group(P<0.05), and the expression amount was proportional to modeling time. Conclusion: Rat OA models are effectively produced. The expression of TLR2, TLR4, and NF-kB are related to the disease duration of OA, which are key factors to OA progression.

参考文献/References:

[1] Chen B,Deng Y,Tan Y,et al.Association between severity of knee osteoar thritis and serum and synovial fluid interleukin 17 concentrations[J].J Int Med Res,2014,42(1):138-144.
[2] 彭伟.膝关节骨性关节炎治疗的研究进展[J].中国社区医师:医学专业,2013,15(1):7-8.
[3] 程少丹,徐菁,王慧芳,等.膝骨关节炎针灸治疗研究进展[J].中国中医骨伤科杂志,2013,21(1):72-74.
[4] Hall M,Doherty S,Courtney P,et al.Ultrasound detected synovial change and pain response following intra-articular injection of corticosteroid and a placebo in symptomatic osteoarthritic knees:a pilot study[J].Ann Rheum Dis,2014,73(8):1590-1591.
[5] Ding Q,Ji XW,Cheng Y,et al.Inhibition of matrix metalloproteinases and inducible nitric oxide synthase by andrographolide in human osteoarthritic chondrocytes[J].Mod Rheumatol,2013,23(6):1124-1132.
[6] 何仁豪.骨性关节炎发病机制及与microRNA相关性研究进展[J].中华实用诊断与治疗杂志,2012,26(11):1045-1047.
[7] 赵喆,王振宇,姜川,等.体外冲击波对兔膝骨性关节炎软骨细胞凋亡的影响[J].实用医学杂志,2012,28(20):3348-3350.
[8] 肖巍,杜晓红,李曙波,等.膝骨关节炎发病机制及腔内治疗概述[J].中国民族民间医药,2013(3):47-48.
[9] Sellam J,Berenbaum F.The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis[J].Nat Rev Rheu-matol,2010,6(11):625-635.
[10] Bondeson J,Blom AB,Wainwright S,et al.The role of synovial macrophages and macrophage produced mediators in driving inflammatory and destructive responses in osteoarthritis[J].Arthritis Rheum,2010,62:647-657.
[11] Reynolds JM,Dong C.Toll-like receptor regulation of effector T lymphocyte function[J].Trends Immunol,2013,34(10):511-519.
[12] Sillat T,Barreto G,Clarijs P,et al.Toll-like receptors in human chondrocytes and osteoarthritic cartilage[J].Acta Orthop,2013,84(6):585-592.
[13] Rannou F.Immune system activation in osteoarthritis[M]//Atlas of Osteoarthritis Berlin:Springer,2014:37-54.
[14] Kawai T,Akira S.The role of pattern-recognition receptors in innate immunity:update on Toll-like receptors[J].Nat Immunol,2010,11(5):373-384.
[15] Piccinini AM,Midwood KS.DAMPening inflammation by modulating TLR signalling[J].Mediators Inflamm,2010.
[16] Willcocks S,Offord V,Seyfert HM,et al.Species-specific PAMP recognition by TLR2 and evidence for species-restricted interaction with Dectin-1[J].J Leukoc Biol,2013,94(3):449-458.
[17] Radstake TR,Roelofs MF,Jenniskens YM,et al.Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation byproinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma[J].Arthritis Rheum,2004,50(12):3856-3865.
[18] Zhang Q,Hui W,Litherland GJ,ea al.Differential Toll-like receptor-dependent collagenase expression in chondrocytes[J].Ann Rheum Dis,2008,67(11):1633-1641.
[19] Campo GM,Avenoso A,Campo S,et al.Molecular size hyaluronan differently modulates toll-like receptor-4 in LPS -induced inflammation in mouse chondrocytes[J].Biochimie,2010,92(2):204-215.
[20] 石慧,王丹彤,乌日嘎,等.TNF-α介导的NF-kB信号通路在类风湿性关节炎血管形成中的作用[J].医学综述,2012,18(15):2397-2400.
[21] Li HQ.Effect of celebrex on the expression of NF-kB in articular cartilage of osteoarthritic rat[J].Modern Journal of Integrated Traditional Chinese and Western Medicine,2014,19.
[22] Tian J,Zhang FJ,Lei GH.Role of integrins and their ligands in osteoarthritic cartilage[J].Rheumatology International May,2015,35(5):787-798.
[23] Dev A,Iyer S,Razani B,et al.NF-kB and innate immunity[J].Curr Top Microbiol Immunol,2011,349:115-143.
[24] Kawai T,Akira S.The role of pattern- recognition receptors in innate immunity:update on Toll-like receptors[J].Nat Immunol,2010,11(5):373-384.
[25] Qu Z,Xiao G.Systematic detection of noncanonical NF-kB activation[J].Methods in Molecular Biology,2015,1280:121-154.
[26] Woo YJ,Yoon BY,Jhun JY,et al.Regulation of B cell activating factor belonging to the TNF family(BAFF)receptor expression by NF-kB signaling in rheumatoid arthritis B cells[J].Exp Mol Med,2011,43(6):350-357.
[27] Myouzen K,Kochi Y,Okada Y,et al.Functional variants in NFKBIE and RTKN2 involved in activation of the NF-κB pathway are associated with rheumatoid arthritis in japanese[J].Plos Genet,2012,8(9):e1002949.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金面上项目(81373662)
北京中医药大学自主选题项目(2014-JYBZZ-XS-171)
更新日期/Last Update: 2016-06-15