椎间盘退变动物模型的研究进展
|
摘要
椎间盘退变是腰痛发生的主要原因,严重影响了人们的生活和工作。尽管具体发病机制尚不明确,但近年来其相关动物模型的研究有了很大的进步。造模方法包括结构损伤、应力改变及基因敲除等,本文综述并讨论了这些方法的优缺点和应用方向,以期为后续的研究奠定理论基础。
Degeneration of intervertebral discs is a major cause of lower back pain that seriously affects quality of life and productivity. Although the specific pathogenesis is still unclear,recent research of related animal models has made great progress. The modeling method include structural damage,stress changes,and gene knockout. In this review,we focus on the advantages and disadvantages of these methods and their applications to establish a theoretical foundation for subsequent research.
Degeneration of intervertebral discs is a major cause of lower back pain that seriously affects quality of life and productivity. Although the specific pathogenesis is still unclear,recent research of related animal models has made great progress. The modeling method include structural damage,stress changes,and gene knockout. In this review,we focus on the advantages and disadvantages of these methods and their applications to establish a theoretical foundation for subsequent research.
引文
[1] van US,Silva-CJ,Oliveira JM,et al. Current strategies for treatment of intervertebral disc degeneration:substitution and regeneration possibilities[J]. Biomater Res,2017,21:22.
[2] Zheng CJ,Chen J. Disc degeneration implies low back pain[J].Theor Biol Med Model,2015,12:24.
[3] Masuda K,Aota Y,Muehleman C,et al. A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture:correlation between the degree of disc injury and radiological and histological appearances of disc degeneration[J]. Spine,2005,30(1):5-14.
[4] Cunha C,Lamas S,Gonalves RM,et al. Joint analysis of IVD herniation and degeneration by rat caudal needle puncture model[J]. J Orthop Res,2017,35(2):258-268.
[5]陈涛,王静成,刘忠军,等.经皮细针穿刺纤维环建立大鼠尾椎椎间盘退变动物模型[J].中国医师杂志,2018,20(3):347-351.Chen T,Wang JC,Liu ZJ,et al. Establishment of a rat caudal disc degeneration model by percutaneous fine-needle aspiration of the fibrous ring[J]. J Chin Physician,2018,20(3):347-351.
[6] Ulrich JA,Liebenberg EC,Thuillier DU,et al. ISSLS prize winner:repeated disc injury causes persistent inflammation[J].Spine,2007,32(25):2812-2819.
[7] Kim JS,Kroin JS,Li X,et al. The rat intervertebral disk degeneration pain model:relationships between biological and structural alterations and pain[J]. Arthritis Res Ther,2011,13(5):R165.
[8] Omlor GW,Nerlich AG,Wilke HJ,et al. A new porcine in vivo animal model of disc degeneration:response of anulus fibrosus cells,chondrocyte-like nucleus pulposus cells,and notochordal nucleus pulposus cells to partial nucleotomy[J]. Spine,2009,34(25):2730-2739.
[9] Xi YM,Kong J,Liu Y,et al. Minimally invasive induction of an early lumbar disc degeneration model in rhesus monkeys[J].Spine,2013,38(10):E579-586.
[10] Yoon SH,Miyazaki M,Hong SW,et al. A porcine model of intervertebral disc degeneration induced by annular injury characterized with magnetic resonance imaging and histopathological findings. Laboratory investigation[J]. J Neurosurg Spine,2008,8(5):450-457.
[11] Yuan W, Che W, Jiang YQ, et al. Establishment of intervertebral disc degeneration model induced by ischemic subendplate in rat tail[J]. Spine J,2015,15(5):1050-1059.
[12] Wei FX,Zhong R,Pan X,et al. Computed tomography-guided sub-end plate injection of pingyangmycin for a novel rabbit model of slowly progressive disc degeneration[J]. Spine J,2019,19(2):e6-e18.
[13] Wei FX,Zhong R,Wang L,et al. Pingyangmycin-induced in vivo lumbar disc degeneration model of rhesus monkeys[J].Spine,2015,40(4):E199-210.
[14]白荣飞,张震,林一峰,等.三种方法建立大鼠腰椎间盘退变模型[J].中国组织工程研究,2018,22(16):2514-2519.Bai RF,Zhang Z,Lin YF,et al. Establishing a rat model of intervertebral disc degeneration using three methods[J]. J Clin Rehabil Tis Eng Res,2018,22(16):2514-2519.
[15] Hutton WC,Ganey TM,Elmer WA,et al. Does long-term compressive loading on the intervertebral disc cause degeneration?[J]. Spine,2000,25(23):2993-3004.
[16] Kang R,Li H,Ringgaard S,et al. Interference in the endplate nutritional pathway causes intervertebral disc degeneration in an immature porcine model[J]. Int Orthop,2014,38(5):1011-1017.
[17] Sugimura T, Kato F, Mimatsu K, et al. Experimental chemonucleolysis with chondroitinase ABC in monkeys[J].Spine,1996,21(2):161-165.
[18] Norcross JP,Lester GE,Weinhold P,et al. An in vivo model of degenerative disc disease[J]. J Orthop Res,2003,21(1):183-188.
[19] Hoogendoorn RJ,Helder MN,Kroeze RJ,et al. Reproducible long-term disc degeneration in a large animal model[J]. Spine,2008,33(9):949-954.
[20] Anderson DG,Li X,Balian G. A fibronectin fragment alters the metabolism by rabbit intervertebral disc cells in vitro[J]. Spine,2005,30(11):1242-1246.
[21] Oegema TR Jr,Johnson SL,Aguiar DJ,et al. Fibronectin and its fragments increase with degeneration in the human intervertebral disc[J]. Spine,2000,25(21):2742-2747.
[22] Lee M,Kim BJ,Lim EJ,et al. Complete Freund’s adjuvantinduced intervertebral discitis as an animal model for discogenic low back pain[J]. Anesth Analg,2009,109(4):1287-1296.
[23] Zhou H,Hou S,Shang W,et al. A new in vivo animal model to create intervertebral disc degeneration characterized by MRI,radiography,CT/discogram,biochemistry,and histology[J].Spine,2007,32(8):864-872.
[24] Luoma K,RiihimaKi H,Luukkonen R,et al. Low back pain in relation to lumbar disc degeneration[J]. Spine,2000,25(4):487-492.
[25] BattiéMC,Videman T,Parent E. Lumbar disc degeneration:epidemiology and genetic influences[J]. Spine, 2004, 29(23):2679-2690.
[26] Cassidy JJ,Hiltner A,Baer E. Hierarchical structure of the intervertebral disc[J]. Connect Tissue Res,1989,23(1):75-88.
[27] Kroeber MW,Unglaub F,Wang H,et al. New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration[J]. Spine,2002,27(23):2684-2690.
[28] Ching CT,Chow DH,Yao FY,et al. The effect of cyclic compression on the mechanical properties of the inter-vertebral disc:An in vivo study in a rat tail model[J]. Clin Biomech,2003,18(3):182-189.
[29] Kim JS,Kroin JS,Li X,et al. The rat intervertebral disk degeneration pain model:relationships between biological and structural alterations and pain[J]. Arthritis Res Ther,2011,13(5):R165.
[30] Maclean JJ,Lee CR,Alini M,et al. Anabolic and catabolic mRNA levels of the intervertebral disc vary with the magnitude and frequency of in vivo dynamic compression[J]. J Orthop Res,2004,22(6):1193-1200.
[31] Lotz JC,Colliou OK,Chin JR,et al. Compression-induced degeneration of the intervertebral disc:an in vivo mouse model and finite-element study[J]. Spine,1998,23(23):2493-2506.
[32]徐海栋,刘晓伟,史新瑞,等.[J].脊柱外科杂志,2017,15(6):348-350,356.Xu HD, Liu XW, Shi XR, et al. Construction of caudate degenerative intervertebral disc model by static pressure in rats[J]. J Spinal Surg,2017,15(6):348-350,356.
[33] Hirata H,Yurube T,Kakutani K,et al. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype[J]. J Orthop Res,2014,32(3):455-463.
[34] Yurube T,Takada T,Suzuki T,et al. Rat tail static compression model mimics extracellular matrix metabolic imbalances of matrix metalloproteinases, aggrecanases, and tissue inhibitors of metalloproteinases in intervertebral disc degeneration[J].Arthritis Res Ther,2012,14(2):R51.
[35] Yurube T, Hirata H, Kakutani K, et al. Notochordal cell disappearance and modes of apoptotic cell death in a rat tail static compression-induced disc degeneration model[J]. Arthritis Res Ther,2014,16(1):R31.
[36] Hutton WC,Murakami H,Li J,et al. The effect of blocking a nutritional pathway to the intervertebral disc in the dog model[J]. J Spinal Disord Tech,2004,17(1):53-63.
[37] Miyagi M,Ishikawa T,Orita S,et al. Disk injury in rats produces persistent increases in pain-related neuropeptides in dorsal root ganglia and spinal cord glia but only transient increases in inflammatory mediators[J]. Spine,2011,36(26):2260-2266.
[38] Gruber HE, Johnson TL, Ingram JA, et al. Autologous intervertebral disc cell implantation:a model using psammomys obesus,the sand rat[J]. Spine,2002,27(15):1626-1633.
[39] Bergknut N,Rutges JP,Kranenburg HJ,et al. The dog as an animal model for intervertebral disc degeneration?[J]. Spine,2012,37(5):351-358.
[40] Cho H,Park SH,Lee S,et al. Snapshot of degenerative aging of porcine intervertebral disc:a model to unravel the molecular mechanisms[J]. Exp Mol Med,2011,43(6):334-340.
[41] Stolworthy DK,Bowden AE,Roeder BL,et al. MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine[J]. J Orthop Res,2015,33(12):1776-1783.
[42] Vo N, Niedernhofer LJ, Nasto LA, et al. An overview of underlying causes and animal models for the study of age-related degenerative disorders of the spine and synovial joints[J]. J Orthop Res,2013,31(6):831-837.
[43] Millecamps M,Czerminski JT,Mathieu AP,et al. Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model[J]. Spine J,2015,15(12):2524-2537.
[44] Bedore J,Sha W,Mc Cann MR,et al. Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2[J]. Arthritis Rheum,2013,65(10):2634-2644.
[45] Phillips KL,Jordan-Mahy N,Nicklin MJ,et al. Interleukin-1receptor antagonist deficient mice provide insights into pathogenesis of human intervertebral disc degeneration[J]. Ann Rheum Dis,2013,72(11):1860-1867.
[46] Mcpherron AC, Lee SJ. Double muscling in cattle due to mutations in the myostatin gene[J]. Proc Natl Acad Sci U S A,1997,94(23):12457-12461.
[47] Kallakuri S,Takebayashi T,Ozaktay AC,et al. The effects of epidural application of allografted nucleus pulposus in rats on cytokine expression,limb withdrawal and nerve root discharge[J]. Eur Spine J,2005,14(10):956-964.
[48]周渝,王玲,陈丙波,等.一种新型大鼠腰椎间盘突出症动物模型的建立[J].中国实验动物学报,2008,16(1):23-26.Zhou Y,Wang L,Chen BB,et al. Development of a new rat model of lumbar intervertebral disc herniation[J]. Acta Lab Anim Sci Sin,2008,16(1):23-26.
[49] Wang D,Nasto LA,Roughley P,et al. Spine degeneration in a murine model of chronic human tobacco smokers[J].Osteoarthritis Cartilage,2012,20(8):896-905.
[50] Zhang D, Jin L, Reames DL, et al. Intervertebral disc degeneration and ectopic bone formation in apolipoprotein E knockout mice[J]. J Orthop Res,2013,31(2):210-217.
[51] Fields AJ,Berg-Johansen B,Metz LN,et al. Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2diabetes[J]. Spine J,2015,15(10):S142-S143.
[52] Chris D,Peter G,Graham J,et al. A review of animal models of intervertebral disc degeneration:pathophysiology,regeneration,and translation to the clinic[J]. Biomed Res Int, 2016,2016:5952165.
[2] Zheng CJ,Chen J. Disc degeneration implies low back pain[J].Theor Biol Med Model,2015,12:24.
[3] Masuda K,Aota Y,Muehleman C,et al. A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture:correlation between the degree of disc injury and radiological and histological appearances of disc degeneration[J]. Spine,2005,30(1):5-14.
[4] Cunha C,Lamas S,Gonalves RM,et al. Joint analysis of IVD herniation and degeneration by rat caudal needle puncture model[J]. J Orthop Res,2017,35(2):258-268.
[5]陈涛,王静成,刘忠军,等.经皮细针穿刺纤维环建立大鼠尾椎椎间盘退变动物模型[J].中国医师杂志,2018,20(3):347-351.Chen T,Wang JC,Liu ZJ,et al. Establishment of a rat caudal disc degeneration model by percutaneous fine-needle aspiration of the fibrous ring[J]. J Chin Physician,2018,20(3):347-351.
[6] Ulrich JA,Liebenberg EC,Thuillier DU,et al. ISSLS prize winner:repeated disc injury causes persistent inflammation[J].Spine,2007,32(25):2812-2819.
[7] Kim JS,Kroin JS,Li X,et al. The rat intervertebral disk degeneration pain model:relationships between biological and structural alterations and pain[J]. Arthritis Res Ther,2011,13(5):R165.
[8] Omlor GW,Nerlich AG,Wilke HJ,et al. A new porcine in vivo animal model of disc degeneration:response of anulus fibrosus cells,chondrocyte-like nucleus pulposus cells,and notochordal nucleus pulposus cells to partial nucleotomy[J]. Spine,2009,34(25):2730-2739.
[9] Xi YM,Kong J,Liu Y,et al. Minimally invasive induction of an early lumbar disc degeneration model in rhesus monkeys[J].Spine,2013,38(10):E579-586.
[10] Yoon SH,Miyazaki M,Hong SW,et al. A porcine model of intervertebral disc degeneration induced by annular injury characterized with magnetic resonance imaging and histopathological findings. Laboratory investigation[J]. J Neurosurg Spine,2008,8(5):450-457.
[11] Yuan W, Che W, Jiang YQ, et al. Establishment of intervertebral disc degeneration model induced by ischemic subendplate in rat tail[J]. Spine J,2015,15(5):1050-1059.
[12] Wei FX,Zhong R,Pan X,et al. Computed tomography-guided sub-end plate injection of pingyangmycin for a novel rabbit model of slowly progressive disc degeneration[J]. Spine J,2019,19(2):e6-e18.
[13] Wei FX,Zhong R,Wang L,et al. Pingyangmycin-induced in vivo lumbar disc degeneration model of rhesus monkeys[J].Spine,2015,40(4):E199-210.
[14]白荣飞,张震,林一峰,等.三种方法建立大鼠腰椎间盘退变模型[J].中国组织工程研究,2018,22(16):2514-2519.Bai RF,Zhang Z,Lin YF,et al. Establishing a rat model of intervertebral disc degeneration using three methods[J]. J Clin Rehabil Tis Eng Res,2018,22(16):2514-2519.
[15] Hutton WC,Ganey TM,Elmer WA,et al. Does long-term compressive loading on the intervertebral disc cause degeneration?[J]. Spine,2000,25(23):2993-3004.
[16] Kang R,Li H,Ringgaard S,et al. Interference in the endplate nutritional pathway causes intervertebral disc degeneration in an immature porcine model[J]. Int Orthop,2014,38(5):1011-1017.
[17] Sugimura T, Kato F, Mimatsu K, et al. Experimental chemonucleolysis with chondroitinase ABC in monkeys[J].Spine,1996,21(2):161-165.
[18] Norcross JP,Lester GE,Weinhold P,et al. An in vivo model of degenerative disc disease[J]. J Orthop Res,2003,21(1):183-188.
[19] Hoogendoorn RJ,Helder MN,Kroeze RJ,et al. Reproducible long-term disc degeneration in a large animal model[J]. Spine,2008,33(9):949-954.
[20] Anderson DG,Li X,Balian G. A fibronectin fragment alters the metabolism by rabbit intervertebral disc cells in vitro[J]. Spine,2005,30(11):1242-1246.
[21] Oegema TR Jr,Johnson SL,Aguiar DJ,et al. Fibronectin and its fragments increase with degeneration in the human intervertebral disc[J]. Spine,2000,25(21):2742-2747.
[22] Lee M,Kim BJ,Lim EJ,et al. Complete Freund’s adjuvantinduced intervertebral discitis as an animal model for discogenic low back pain[J]. Anesth Analg,2009,109(4):1287-1296.
[23] Zhou H,Hou S,Shang W,et al. A new in vivo animal model to create intervertebral disc degeneration characterized by MRI,radiography,CT/discogram,biochemistry,and histology[J].Spine,2007,32(8):864-872.
[24] Luoma K,RiihimaKi H,Luukkonen R,et al. Low back pain in relation to lumbar disc degeneration[J]. Spine,2000,25(4):487-492.
[25] BattiéMC,Videman T,Parent E. Lumbar disc degeneration:epidemiology and genetic influences[J]. Spine, 2004, 29(23):2679-2690.
[26] Cassidy JJ,Hiltner A,Baer E. Hierarchical structure of the intervertebral disc[J]. Connect Tissue Res,1989,23(1):75-88.
[27] Kroeber MW,Unglaub F,Wang H,et al. New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration[J]. Spine,2002,27(23):2684-2690.
[28] Ching CT,Chow DH,Yao FY,et al. The effect of cyclic compression on the mechanical properties of the inter-vertebral disc:An in vivo study in a rat tail model[J]. Clin Biomech,2003,18(3):182-189.
[29] Kim JS,Kroin JS,Li X,et al. The rat intervertebral disk degeneration pain model:relationships between biological and structural alterations and pain[J]. Arthritis Res Ther,2011,13(5):R165.
[30] Maclean JJ,Lee CR,Alini M,et al. Anabolic and catabolic mRNA levels of the intervertebral disc vary with the magnitude and frequency of in vivo dynamic compression[J]. J Orthop Res,2004,22(6):1193-1200.
[31] Lotz JC,Colliou OK,Chin JR,et al. Compression-induced degeneration of the intervertebral disc:an in vivo mouse model and finite-element study[J]. Spine,1998,23(23):2493-2506.
[32]徐海栋,刘晓伟,史新瑞,等.[J].脊柱外科杂志,2017,15(6):348-350,356.Xu HD, Liu XW, Shi XR, et al. Construction of caudate degenerative intervertebral disc model by static pressure in rats[J]. J Spinal Surg,2017,15(6):348-350,356.
[33] Hirata H,Yurube T,Kakutani K,et al. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype[J]. J Orthop Res,2014,32(3):455-463.
[34] Yurube T,Takada T,Suzuki T,et al. Rat tail static compression model mimics extracellular matrix metabolic imbalances of matrix metalloproteinases, aggrecanases, and tissue inhibitors of metalloproteinases in intervertebral disc degeneration[J].Arthritis Res Ther,2012,14(2):R51.
[35] Yurube T, Hirata H, Kakutani K, et al. Notochordal cell disappearance and modes of apoptotic cell death in a rat tail static compression-induced disc degeneration model[J]. Arthritis Res Ther,2014,16(1):R31.
[36] Hutton WC,Murakami H,Li J,et al. The effect of blocking a nutritional pathway to the intervertebral disc in the dog model[J]. J Spinal Disord Tech,2004,17(1):53-63.
[37] Miyagi M,Ishikawa T,Orita S,et al. Disk injury in rats produces persistent increases in pain-related neuropeptides in dorsal root ganglia and spinal cord glia but only transient increases in inflammatory mediators[J]. Spine,2011,36(26):2260-2266.
[38] Gruber HE, Johnson TL, Ingram JA, et al. Autologous intervertebral disc cell implantation:a model using psammomys obesus,the sand rat[J]. Spine,2002,27(15):1626-1633.
[39] Bergknut N,Rutges JP,Kranenburg HJ,et al. The dog as an animal model for intervertebral disc degeneration?[J]. Spine,2012,37(5):351-358.
[40] Cho H,Park SH,Lee S,et al. Snapshot of degenerative aging of porcine intervertebral disc:a model to unravel the molecular mechanisms[J]. Exp Mol Med,2011,43(6):334-340.
[41] Stolworthy DK,Bowden AE,Roeder BL,et al. MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine[J]. J Orthop Res,2015,33(12):1776-1783.
[42] Vo N, Niedernhofer LJ, Nasto LA, et al. An overview of underlying causes and animal models for the study of age-related degenerative disorders of the spine and synovial joints[J]. J Orthop Res,2013,31(6):831-837.
[43] Millecamps M,Czerminski JT,Mathieu AP,et al. Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model[J]. Spine J,2015,15(12):2524-2537.
[44] Bedore J,Sha W,Mc Cann MR,et al. Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2[J]. Arthritis Rheum,2013,65(10):2634-2644.
[45] Phillips KL,Jordan-Mahy N,Nicklin MJ,et al. Interleukin-1receptor antagonist deficient mice provide insights into pathogenesis of human intervertebral disc degeneration[J]. Ann Rheum Dis,2013,72(11):1860-1867.
[46] Mcpherron AC, Lee SJ. Double muscling in cattle due to mutations in the myostatin gene[J]. Proc Natl Acad Sci U S A,1997,94(23):12457-12461.
[47] Kallakuri S,Takebayashi T,Ozaktay AC,et al. The effects of epidural application of allografted nucleus pulposus in rats on cytokine expression,limb withdrawal and nerve root discharge[J]. Eur Spine J,2005,14(10):956-964.
[48]周渝,王玲,陈丙波,等.一种新型大鼠腰椎间盘突出症动物模型的建立[J].中国实验动物学报,2008,16(1):23-26.Zhou Y,Wang L,Chen BB,et al. Development of a new rat model of lumbar intervertebral disc herniation[J]. Acta Lab Anim Sci Sin,2008,16(1):23-26.
[49] Wang D,Nasto LA,Roughley P,et al. Spine degeneration in a murine model of chronic human tobacco smokers[J].Osteoarthritis Cartilage,2012,20(8):896-905.
[50] Zhang D, Jin L, Reames DL, et al. Intervertebral disc degeneration and ectopic bone formation in apolipoprotein E knockout mice[J]. J Orthop Res,2013,31(2):210-217.
[51] Fields AJ,Berg-Johansen B,Metz LN,et al. Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2diabetes[J]. Spine J,2015,15(10):S142-S143.
[52] Chris D,Peter G,Graham J,et al. A review of animal models of intervertebral disc degeneration:pathophysiology,regeneration,and translation to the clinic[J]. Biomed Res Int, 2016,2016:5952165.