MMP-1、TIMP-1在不同年龄患者及不同退变程度椎间盘纤维环和髓核组织中的表达
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摘要
目的探究基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)、组织金属蛋白酶抑制因子-1(tissue inhibitor of metalloproteinase-1,TIMP-1)在不同年龄患者及不同退变程度椎间盘纤维环和髓核组织中的表达。方法选择2016年1月至2017年1月于本院行腰椎间盘切除术的腰椎间盘突出症患者120例为研究对象,将其中40例中年患者纳入中年组,40例老年患者纳入老年组,40例青年患者纳入青年组,采用免疫组织化学法检测并比较三组患者椎间盘纤维环和髓核组织中MMP-1、TIMP-1阳性表达率,同时比较各组内纤维环和髓核组织中MMP-1、TIMP-1阳性表达率。结果纤维环和髓核组织中MMP-1和TIMP-1阳性表达率均为老年组>中年组>青年组(P_均<0.05),且三组患者髓核组织中MMP-1、TIMP-1阳性表达率均显著高于其在纤维环组织中的阳性表达率(P_均<0.05)。三组患者髓核及纤维环组织中MMP-1、TIMP-1阳性表达率均为游离型>脱出型>突出型(P_均<0.05)。Spearman相关性分析显示:MMP-1和TIMP-1阳性表达率与患者年龄、椎间盘退变程度均呈正相关(P_均<0.05)。结论 MMP-1和TIMP-1在退变椎间盘组织中的表达与患者年龄及椎间盘退变程度均呈正相关,且在髓核处较纤维环处变化更明显,MMP-1和TIMP-1可作为判断椎间盘退变程度的重要标志物。
Objective To investigate the expression of matrix metalloproteinase 1(MMP-1) and tissue inhibitor of metallop roteinase 1(TIMP-1) in annulus fibrosus and nucleus pulposus of degenerated intervertebral discs in different degrees and age. MethodFrom January 2016 to January 2017, 120 patients with lumbar disc herniation treated by lumbar discectomy were divided into middleaged group(n = 40), old-age group(n = 40) and youth group(n = 40). Immunohistochemistry was used to detect and compare the expression of MMP-1 and TIMP-1 of three groups, and to compare the expression of MMP-1 and TIMP-1 in different degeneration of intervertebral disc. Result The positive rates of MMP-1 and TIMP-1 expression in annulus fibrosus and nucleus pulposus were: elderly group > middle-aged group > young group(P_(all)< 0.05). The positive rates of MMP-1 and TIMP-1 in nucleus pulposus of the three groups were significantly higher than those in annulus fibrosus(P_(all)< 0.05). The positive rates of MMP-1 and TIMP-1 in nucleus pulposus and annulus fibrosus of the three groups were: free type > exfoliative type > prominent type(P_(all)< 0.05). Spearman correlation analysis showed that the positive rates of MMP-1 and TIMP-1 were positively correlated with age and degree of degeneration(P_(all)< 0.05). Conclusion The positive rate of MMP-1 and TIMP-1 expression are positively corre lated with ages and the degree of degeneration. The expression in nucleus pulposus is higher than that in annulus fibrosus. It illustrates that MMP-1 and TIMP-1 are involved in the degeneration of intervertebral disc, and can be the important indicator of prognosis.
Objective To investigate the expression of matrix metalloproteinase 1(MMP-1) and tissue inhibitor of metallop roteinase 1(TIMP-1) in annulus fibrosus and nucleus pulposus of degenerated intervertebral discs in different degrees and age. MethodFrom January 2016 to January 2017, 120 patients with lumbar disc herniation treated by lumbar discectomy were divided into middleaged group(n = 40), old-age group(n = 40) and youth group(n = 40). Immunohistochemistry was used to detect and compare the expression of MMP-1 and TIMP-1 of three groups, and to compare the expression of MMP-1 and TIMP-1 in different degeneration of intervertebral disc. Result The positive rates of MMP-1 and TIMP-1 expression in annulus fibrosus and nucleus pulposus were: elderly group > middle-aged group > young group(P_(all)< 0.05). The positive rates of MMP-1 and TIMP-1 in nucleus pulposus of the three groups were significantly higher than those in annulus fibrosus(P_(all)< 0.05). The positive rates of MMP-1 and TIMP-1 in nucleus pulposus and annulus fibrosus of the three groups were: free type > exfoliative type > prominent type(P_(all)< 0.05). Spearman correlation analysis showed that the positive rates of MMP-1 and TIMP-1 were positively correlated with age and degree of degeneration(P_(all)< 0.05). Conclusion The positive rate of MMP-1 and TIMP-1 expression are positively corre lated with ages and the degree of degeneration. The expression in nucleus pulposus is higher than that in annulus fibrosus. It illustrates that MMP-1 and TIMP-1 are involved in the degeneration of intervertebral disc, and can be the important indicator of prognosis.
引文
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[14]Wang WJ,Yu XH,Wang C,et al.MMPs and ADAMTSs in intervertebral disc degeneration[J].Clin Chim Acta,2015,448:238-246.
[15]流小舟,徐海栋,周光新,等.椎间盘退变中基质金属蛋白酶作用的研究进展[J].医学研究生学报,2015,28(11):1213-1217.
[16]邓斌,王叶新,孟纯阳.椎间盘退变患者血清及髓核组织中基质金属蛋白酶1及抑制剂1的表达[J].中国组织工程研究,2016,20(29):4303-4310.
[17]宋庆鑫,王琨,唐沂星,等.金属蛋白酶类及其抑制剂在椎间盘退变中作用研究进展[J].第二军医大学学报,2015,36(2):201-205.
[18]陈思进,廖歆,王倚天,等.椎间盘退变性疾病相关基因的研究进展[J].骨科,2015,6(4):220-223.
[19]Vo NV,Hartman RA,Patil PR,et al.Molecular mechanisms of biological aging in intervertebral discs[J].J Orthopaedic Res,2016,34(8):1289-1306.
[2]Tisherman R,Coelho P,Phillibert D,et al.NF-κB Signaling Pathway in Controlling Intervertebral Disc Cell Response to Inflammatory and Mechanical Stressors[J].Phy Ther,2016,96(5):704-711.
[3]Teraguchi M,Yoshimura N,Hashizume H,et al.Metabolic Syndrome Components Are Associated with Intervertebral Disc Degeneration:The Wakayama Spine Study[J].PLoS One,2016,11(2):e0147565.
[4]Donizy P,Rudno-Rudzinska J,Kaczorowski M,et al.Disrupted Balance of MMPs/TIMPs in Gastric Carcinogenesis-Paradoxical Low MMP-2 Expression in Tumor and Stromal Compartments as a Potential Marker of Unfavorable Outcome[J].Cancer Invest,2015,33(7):286-293.
[5]Qu H,Li J,Wu LD,et al.Trichostatin A increases the TIMP-1/MMP ratio to protect against osteoarthritis in an animal model of the disease[J].Mol Med Rep,2016,14(3):2423-2430.
[6]梁亮,甫拉提·买买提,张健,等.后路单侧和双侧内固定治疗腰椎间盘突出症临床疗效[J].中华实用诊断与治疗杂志,2015,29(2):148-151.
[7]李杰,马超,李益明,等.椎板开窗髓核摘除纤维环缝合术与单纯髓核摘除术对青少年腰椎间盘突出症的早期疗效[J].中华医学杂志,2016,96(32):4073-4077.
[8]Wang W,Hao J,Zheng S,et al.Association Between Cartilage Intermediate Layer Protein and Degeneration of Intervertebral Disc:A Meta-analysis[J].Spine,2016,41(20):E1244-E1248.
[9]Schleich C,Müller-Lutz A,Zimmermann L,et al.Biochemical imaging of cervical intervertebral discs with glycosaminogly can chemical exchange saturation transfer magnetic resonance imaging:feasibility and initial results[J].Skeletal Radiol,2016,45(1):79-85.
[10]俞佳斌,王宸,马雪倩,等.椎间盘退行性变机制的研究进展[J].脊柱外科杂志,2017,15(6):374-379.
[11]Molinos M,Almeida CR,Caldeira J,et al.Inflammation in interv ertebral disc degeneration and regeneration[J].J R Soc Inte rface,2015,12(104):20141191.
[12]林建平,陈少清,林先钊,等.“三步五法”对椎间盘胞外基质系统的调控作用[J].中华中医药杂志,2015,30(11):4087-4090.
[13]邱晨生,沈娜娜,岳斌,等.慢病毒介导TGFβ3和TIMP1体外联合感染对人退变椎间盘髓核细胞的影响[J].青岛大学医学院学报,2015,51(4):408-410.
[14]Wang WJ,Yu XH,Wang C,et al.MMPs and ADAMTSs in intervertebral disc degeneration[J].Clin Chim Acta,2015,448:238-246.
[15]流小舟,徐海栋,周光新,等.椎间盘退变中基质金属蛋白酶作用的研究进展[J].医学研究生学报,2015,28(11):1213-1217.
[16]邓斌,王叶新,孟纯阳.椎间盘退变患者血清及髓核组织中基质金属蛋白酶1及抑制剂1的表达[J].中国组织工程研究,2016,20(29):4303-4310.
[17]宋庆鑫,王琨,唐沂星,等.金属蛋白酶类及其抑制剂在椎间盘退变中作用研究进展[J].第二军医大学学报,2015,36(2):201-205.
[18]陈思进,廖歆,王倚天,等.椎间盘退变性疾病相关基因的研究进展[J].骨科,2015,6(4):220-223.
[19]Vo NV,Hartman RA,Patil PR,et al.Molecular mechanisms of biological aging in intervertebral discs[J].J Orthopaedic Res,2016,34(8):1289-1306.