腰椎力学失衡与椎间盘退变联系的实验研究家兔腰椎力学失衡与椎间盘退变联系的机理研究
|
摘要
目的：以生物力学理论为指导，造出家兔腰椎生物力学失衡模型，利用组织学和免疫学对造模后的椎间盘组织进行观察和检测，从而探讨腰椎生物力学失衡与腰椎间盘组织退变之间的联系。阐明腰椎生物力学失衡导致腰椎间盘退变、突出和腰椎退行性病变的发病机制，为腰椎退行性病变和腰椎间盘退变及突出症的防治提供理论依据。
方法：日本大耳白兔32只，10～12月龄，体重2.5～3.0kg。随机分为动力失衡模型组、静力失衡模型组、动静力失衡模型组和正常对照组，每组各8只。通过手术切除家兔腰背竖脊肌和背阔肌，建立动力失衡模型；手术切断棘上韧带、棘间韧带，建立静力失衡模型；手术同时切断上述肌肉和韧带，建立动静力失衡模型。对照组只切开皮肤，不做肌肉切断及韧带切除。术后常规饲养3个月，处死试验动物，分别取出L3、L4、L5椎间盘组织，进行病理学观察和生化检测。
结果：
1、组织形态学观察：结果显示三个模型组的椎间盘可见纤维环出现裂隙，细胞排列不规则，甚至纤维环的正常结构消失；髓核出现皱缩或变小，髓核内细胞减少，部分髓核组织突出纤维环裂隙内；组织形态学评判椎间盘退变的程度，静力失衡组、动静力失衡组分值高于对照组(P＜0.05和P＜0.01)。
2、生化检查：前列腺素PGE2和6-酮-PGF1 α含量，胶原酶活性测定。与正常对照组相比较，动力失衡模型组、静力失衡模型组、动静力失衡模型组PGE2和6-keto-PGFla含量明显升高(P＜0.05或P＜0.01)；胶原酶活性明显升高(P＜0.05或P＜0.01)。
结论：
1、动力和静力平衡系统对家兔腰椎的稳定和生理功能有着重要作用；
2、家兔腰椎生物力学失衡可导致椎间盘退变。
Objective: on the guidance of the vitodynamics theories ,we set up the rabbit model of lumbar vertebrae vitodynamic imbalance , and use the histomorphology and immunology theory to detect and analyze the intervertebral disc tissue after the model has been built, and investigate the connection of lumbar vertebrae vitodynamic disbalance and lumbar intervertebral disc tissue cataplasis. Otherwise, through the analysis of experimental data, pathomechanism was explained that lumbar vertebrae vitodynamic disbalance lead to lumbar intervertebral disc tissue cataplasis、protrusion and lumbar spine degenerative disease process, to guide the prevention and cure of lumbar degenerative disease process and lumbar intervertebral disc tissue cataplasis, lumbar disc herniation ,at the same time to provide functional exercise the theory basis.
Method: 32 rabbits, half female and half male,10～12 months old, were randomly divided into 4 groups : dynamia disbalance model group、static force unbalance model group、dynamia and static force disbalance model group 、control group. Each group has 8 rabbits. Cutting transversally erector spinae and musculus latissimus dorsi to set up the dynamia disbalance model. Cutting ligament supraspinale、interspinal ligaments and ligamentum transversum to set up the static force unbalance model. The dynamia and static force disbalance model was set up by cutting all the musles and ligaments mentinged previously. Control group had the other 8 rabbits that were only cut skin . Penicillin was used through intramuscular injection in erery rabbit for one week after the model had been set up. Meanwhile raising the rabbits 3 monthes , then killing the animals and dislodging the intervertebral disc tissues of lumbar 3 and lumbar 4 and lumbar 5. At last making pathologic observation and biochemical detection.
Results:
1.Through the rabbit anatomical observation, dentifying the local anatomic structure of lumbar spine.
2.Through tectological observation we found: annular fibrosus was rimous of discus intervertebralis in model groups, array was gently irregular, even the normal structure of annular fibrosus was disappear, being fibrotic; and nucleus pulposus was
方法：日本大耳白兔32只，10～12月龄，体重2.5～3.0kg。随机分为动力失衡模型组、静力失衡模型组、动静力失衡模型组和正常对照组，每组各8只。通过手术切除家兔腰背竖脊肌和背阔肌，建立动力失衡模型；手术切断棘上韧带、棘间韧带，建立静力失衡模型；手术同时切断上述肌肉和韧带，建立动静力失衡模型。对照组只切开皮肤，不做肌肉切断及韧带切除。术后常规饲养3个月，处死试验动物，分别取出L3、L4、L5椎间盘组织，进行病理学观察和生化检测。
结果：
1、组织形态学观察：结果显示三个模型组的椎间盘可见纤维环出现裂隙，细胞排列不规则，甚至纤维环的正常结构消失；髓核出现皱缩或变小，髓核内细胞减少，部分髓核组织突出纤维环裂隙内；组织形态学评判椎间盘退变的程度，静力失衡组、动静力失衡组分值高于对照组(P＜0.05和P＜0.01)。
2、生化检查：前列腺素PGE2和6-酮-PGF1 α含量，胶原酶活性测定。与正常对照组相比较，动力失衡模型组、静力失衡模型组、动静力失衡模型组PGE2和6-keto-PGFla含量明显升高(P＜0.05或P＜0.01)；胶原酶活性明显升高(P＜0.05或P＜0.01)。
结论：
1、动力和静力平衡系统对家兔腰椎的稳定和生理功能有着重要作用；
2、家兔腰椎生物力学失衡可导致椎间盘退变。
Objective: on the guidance of the vitodynamics theories ,we set up the rabbit model of lumbar vertebrae vitodynamic imbalance , and use the histomorphology and immunology theory to detect and analyze the intervertebral disc tissue after the model has been built, and investigate the connection of lumbar vertebrae vitodynamic disbalance and lumbar intervertebral disc tissue cataplasis. Otherwise, through the analysis of experimental data, pathomechanism was explained that lumbar vertebrae vitodynamic disbalance lead to lumbar intervertebral disc tissue cataplasis、protrusion and lumbar spine degenerative disease process, to guide the prevention and cure of lumbar degenerative disease process and lumbar intervertebral disc tissue cataplasis, lumbar disc herniation ,at the same time to provide functional exercise the theory basis.
Method: 32 rabbits, half female and half male,10～12 months old, were randomly divided into 4 groups : dynamia disbalance model group、static force unbalance model group、dynamia and static force disbalance model group 、control group. Each group has 8 rabbits. Cutting transversally erector spinae and musculus latissimus dorsi to set up the dynamia disbalance model. Cutting ligament supraspinale、interspinal ligaments and ligamentum transversum to set up the static force unbalance model. The dynamia and static force disbalance model was set up by cutting all the musles and ligaments mentinged previously. Control group had the other 8 rabbits that were only cut skin . Penicillin was used through intramuscular injection in erery rabbit for one week after the model had been set up. Meanwhile raising the rabbits 3 monthes , then killing the animals and dislodging the intervertebral disc tissues of lumbar 3 and lumbar 4 and lumbar 5. At last making pathologic observation and biochemical detection.
Results:
1.Through the rabbit anatomical observation, dentifying the local anatomic structure of lumbar spine.
2.Through tectological observation we found: annular fibrosus was rimous of discus intervertebralis in model groups, array was gently irregular, even the normal structure of annular fibrosus was disappear, being fibrotic; and nucleus pulposus was
引文
1．裴仁全．椎间盘退变的MRI与病理学研究．中华放射学杂志．1995，29(3)：175．
2. Kelsey JI. An epidemiologicai study of the relationship between occupations and acute herniated lumbar intervertebral discs[J]. Int J Epidemioi, 1975,4(3):197～205.
3. Frymoyer JVV, Pope MH, Clements JH, et al. Risk factors in low-back pain. An epidemiological survey[J]. J Bone Joint Surg Am, 1983,65(2):213～218.
4. Kelsey JL,Githens PB,White AA 3rd,et al. An epidemiologic study of lifting and twisting on the job and risk for acute prolapsed lumbar intervertebral disc[J]. J Orthop Res,1984,2(1):61～66.
5. Videman T, Nurminen M, Troup JD, et al. Lumbar spinal pathology in cadaveric material in relation to history of back pain, occupation and physical loading[J].Spine, 1990,15:725～740.
6. Oibson MJ, Bucicley J, Mawhinney R, et al. Magnetic resonance imaging and discography in the diagnosis of disc degeneration. A comparative study of 50 discs. The Journal Of Bone And Joint Surgery.1986, 68(3): 369～373.
7．郭洪河，付维林．CT对腰椎退行性变的诊断价值．山西医药杂志，2005，34(6)：474～475．
8．任先军，彭城．椎体终板形态与椎间盘营养的关系．中国矫形外科杂志．2002，9(7)：705．
9. Kang JD, Georgescu HI, Mclntyre-Larkin L, et al. Herniated lumbar intervertebral discs spontaneously produce matrix metailoproteinases, nitric oxide, interleukin-6, and prostaglandin E2.spine, 1996, 21(3): 271-277.
10. Willburger RE, Wittenberg RH. Prostaglandin release from lumbar disc and facet joint tissue. Spine, 1994, 19(18): 2068-2070.
11．彭宝淦，施杞．贾连顺，等．退变颈椎间盘中胶原酶活性变化。颈腰痛杂志．1999，20(4)：248-250．
12．王方，黄淦堂，沈珊安，等。腰椎组织胶原酶活性测定及临床意义．临床骨科杂志．1998；1(2)：92-93．
13. Macnab I, Haris RI, Laurinc.Verte bral Lipping in the lumbar spine.J Bonea and Joint Surg1956; 31(8): 456.
14．戴力扬，贾连顺，徐印钦．腰椎屈伸活动的生物力学与临床意义．生物医学工程学杂志．1993，10(2)：175-181．
15．戴力扬，等．腰段脊柱的三维有限元模型．生物力学，1991；6：42．
16．戴力扬，等．人类腰椎活动阶段的力学模型．解剖学报．1990；21：337．
17．戴力扬，等．腰椎椎体应力分布的三维有限元分析．中国临床解剖学杂志．1991；9，44．
18．戴力扬，等．腰椎屈伸活动对腰椎应力分布的影响．中国临床解剖学杂志．1990；8，36．
19．施杞，郝永强，彭宝淦，等．动静力平衡失调与颈椎病．上海中医药大学学报．1999，13(1)：52-56．
20．姜宏，施杞，王以进，等．颈椎稳定性的生物力学实验研究．中国脊柱脊髓杂志．1999，9(5)：257-259．
21．余家阔，吴毅文，汪发贵，等．实验性颈椎应力应变分布改变对颈椎组织结构的影响．中华外科杂志 1993；38(4)：927．
22．余家阔，吴毅文，戴先进，等．颈椎生物力学发病机制的实验研究．安徽医科大学学报 1990；1：47．
23. Miyamoto S, Yonenobu K, Ono K. Experimental cervical spondylosis in the mouse. Spine 1991,16(10):495-500.
24. Thompson JP, Pearce RH, Schechter MT, et al. Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc.Spine, 1990,15(5):411-415.
25. Ariga K, Miyarnoto S. Nakase T, et al. The relationship between apoptosis of endplate chondrocytes and aging and degeneration of the intervertebral disc.Spine,2001, 26:2414-2420.
26. van Akkerveeken PF, O'Brien JP, Park WM. Experimentally induced hypermobility in the lumbar spine.A pathologic and radiologic study of the posterior ligament and annulus fibrosus Spine 1979,4(3):236.
27. Meachim, G Fine structure of juvenile human nucleus pulposus. J Anat 1970,107(2):337～350.
28. Trout JJ, Buckwalter JA. Ultra.structure of the human interverbral discs.1.changes in notochordal cells with age. Tissue Cell 1982,14(2):396.
29. Krajickova J,Polakova R, Smetana K,et al. Age-dependent changes in proteoglycan biosynthesis in human intervertebral discs. Folia Bioi(Praha). 1995,41(1):41～51.
30．王文岳，刘金华，周强，等．腰椎间盘突出症与前列腺素E2的相关性研究[J]．贵阳中医学院报，2005，27(2)：25～28．
31. O'Donnell JL, O'Donnell AL.Prostaglandin E2 content in herniated lumbar disc disease [3].Spine, 1996,21(14): 1653～1656.
32．亓建洪，王俊勤，鲁玉来，等．影响椎间盘退变生物化学改变的因素[J]．中国矫形外科杂志．2002，9(4)：381～382．
33. Rannou F, Corvol MT, Hudry C, et al. Sensitivity of annulus fibrosus cells to interleuikin 1β.Comparison with articular chondrocytes [J].Spine, 2000, 25(1): 17～23.
34. Burke JG, Waston RW, McCormack D, et al. lntervertebral discs which cause low back pain secrete high levels of proinflammatory mediators [J].J Bone Joint Surg Br,2002,84(2): 196～201.
35. Kanemoto M, Hukuda S, Komiya Y, et al. Immunohistochemical study of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 human intervertebral discs [J] .Spine, 1996, 21(1):1～8.
36. Liu J,Roughley PJ.Mort JS. Identification of human intervertebral disc stromelysin and its involvement in matrix degradation. J Orthop Res, 1991,9(4):568～575.
37. Chelberg MK,Banks GM,Geiger DF, et al. Identification of heterogeneous cell populations in normal human intervertebral disc. J Anat, 1995; 186(1):43～53.
38. Sakuma M, Fujii N, Takahashi T, et al .Effect of chondroitinase ABC on matrix metalloproteinases and inflammatory mediators produced by intervertebral disc of rabbit in vitro[J].Spine,2002,27(6):576～580.
39. Gruber HE, Hanley EN Jr. Analysis of aging and degeneration of the human intervertebral disc. Comparison of surgical specimens with normal controls[J].Spine, 1998,23(7):751～757.
40. Kang JD, Stefanovic-Racic M, Mclntyre LA, et al.Toward a Biochemical Understanding of human intervertebral disc degeneration and herniation.Spine, 1997,22(10):1065-1073.
41．戴力扬，等．中国临床应用解剖学杂志．1989，7：117．
42. Kuga N, Kawabuchi M. Histology of intervertebral disc protrusion: an experimental study using an aged rat model. Spine.2001,26(17):379～84.
43. van Deursen DL, Snijders CJ, Kingma I et al. In vitro torsion-induced stress distribution changes in porcine intervertebral discs. Spine 2001,26(23):2552～2586.
44．娄明武，褚丽娟，王英久，等．腰椎间盘的生物力学研究．1999，33(10)：713～715．
45. Farfan HF, Huberdeau RM, Dubow HI. The biomechanical study on the lumbar intervertebral discs in 182 cadavers. J Bone Joint Surg Am. 1972,54(3):492～510.
46. Lotz JC, Chin JR. lntervertebral disc cell death is dependent on the magnitude and duration of spinal loading [J].Spine,2000,25(12): 1477～1483.
47. Chiu EJ, Newitt DC, Segal MR et al. Magnetic resonance imaging measurement of relaxation and water diffusion in the human lumbar intervertebral disc under compression in vitro. Spine 2001,26(19):437～444.
48. Elfervig MK, Minchew JT, Francke E.IL-1 beta sensitizes intervertebral disc annulus cells to fluid-induced shear stress. J Cell Biochem.2001,82(2):290～298.
49．彭宝淦，贾连顺，施杞，等．软骨终板钙化在椎间盘退变过程中的作用机理．中国矫形外科杂志．2000，7(2)：147-150．
50. Kerttula LI, Serlo WS, Tervonen OA et al. Post-traumatic findings of the spine after earlier vertebral fracture in young patients: clinical and MRI study. Spine 2000, 25(9): 1104～1108.
51．陈立，詹红生，应航，等．长时间异常应力负荷下兔颈椎间盘的组织病理学观察．中国骨伤，2003，16(6)：374～375．
52. Kazarian LE. Creep characteristics of the human spinal column. Orthop Clin North Am, 1975, 6(1):3～18.
53．施杞，彭宝淦，贾连顺．椎体骨赘形成机理的实验研究．中国矫形外科杂志，1997，4(5)，397～398．
2. Kelsey JI. An epidemiologicai study of the relationship between occupations and acute herniated lumbar intervertebral discs[J]. Int J Epidemioi, 1975,4(3):197～205.
3. Frymoyer JVV, Pope MH, Clements JH, et al. Risk factors in low-back pain. An epidemiological survey[J]. J Bone Joint Surg Am, 1983,65(2):213～218.
4. Kelsey JL,Githens PB,White AA 3rd,et al. An epidemiologic study of lifting and twisting on the job and risk for acute prolapsed lumbar intervertebral disc[J]. J Orthop Res,1984,2(1):61～66.
5. Videman T, Nurminen M, Troup JD, et al. Lumbar spinal pathology in cadaveric material in relation to history of back pain, occupation and physical loading[J].Spine, 1990,15:725～740.
6. Oibson MJ, Bucicley J, Mawhinney R, et al. Magnetic resonance imaging and discography in the diagnosis of disc degeneration. A comparative study of 50 discs. The Journal Of Bone And Joint Surgery.1986, 68(3): 369～373.
7．郭洪河，付维林．CT对腰椎退行性变的诊断价值．山西医药杂志，2005，34(6)：474～475．
8．任先军，彭城．椎体终板形态与椎间盘营养的关系．中国矫形外科杂志．2002，9(7)：705．
9. Kang JD, Georgescu HI, Mclntyre-Larkin L, et al. Herniated lumbar intervertebral discs spontaneously produce matrix metailoproteinases, nitric oxide, interleukin-6, and prostaglandin E2.spine, 1996, 21(3): 271-277.
10. Willburger RE, Wittenberg RH. Prostaglandin release from lumbar disc and facet joint tissue. Spine, 1994, 19(18): 2068-2070.
11．彭宝淦，施杞．贾连顺，等．退变颈椎间盘中胶原酶活性变化。颈腰痛杂志．1999，20(4)：248-250．
12．王方，黄淦堂，沈珊安，等。腰椎组织胶原酶活性测定及临床意义．临床骨科杂志．1998；1(2)：92-93．
13. Macnab I, Haris RI, Laurinc.Verte bral Lipping in the lumbar spine.J Bonea and Joint Surg1956; 31(8): 456.
14．戴力扬，贾连顺，徐印钦．腰椎屈伸活动的生物力学与临床意义．生物医学工程学杂志．1993，10(2)：175-181．
15．戴力扬，等．腰段脊柱的三维有限元模型．生物力学，1991；6：42．
16．戴力扬，等．人类腰椎活动阶段的力学模型．解剖学报．1990；21：337．
17．戴力扬，等．腰椎椎体应力分布的三维有限元分析．中国临床解剖学杂志．1991；9，44．
18．戴力扬，等．腰椎屈伸活动对腰椎应力分布的影响．中国临床解剖学杂志．1990；8，36．
19．施杞，郝永强，彭宝淦，等．动静力平衡失调与颈椎病．上海中医药大学学报．1999，13(1)：52-56．
20．姜宏，施杞，王以进，等．颈椎稳定性的生物力学实验研究．中国脊柱脊髓杂志．1999，9(5)：257-259．
21．余家阔，吴毅文，汪发贵，等．实验性颈椎应力应变分布改变对颈椎组织结构的影响．中华外科杂志 1993；38(4)：927．
22．余家阔，吴毅文，戴先进，等．颈椎生物力学发病机制的实验研究．安徽医科大学学报 1990；1：47．
23. Miyamoto S, Yonenobu K, Ono K. Experimental cervical spondylosis in the mouse. Spine 1991,16(10):495-500.
24. Thompson JP, Pearce RH, Schechter MT, et al. Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc.Spine, 1990,15(5):411-415.
25. Ariga K, Miyarnoto S. Nakase T, et al. The relationship between apoptosis of endplate chondrocytes and aging and degeneration of the intervertebral disc.Spine,2001, 26:2414-2420.
26. van Akkerveeken PF, O'Brien JP, Park WM. Experimentally induced hypermobility in the lumbar spine.A pathologic and radiologic study of the posterior ligament and annulus fibrosus Spine 1979,4(3):236.
27. Meachim, G Fine structure of juvenile human nucleus pulposus. J Anat 1970,107(2):337～350.
28. Trout JJ, Buckwalter JA. Ultra.structure of the human interverbral discs.1.changes in notochordal cells with age. Tissue Cell 1982,14(2):396.
29. Krajickova J,Polakova R, Smetana K,et al. Age-dependent changes in proteoglycan biosynthesis in human intervertebral discs. Folia Bioi(Praha). 1995,41(1):41～51.
30．王文岳，刘金华，周强，等．腰椎间盘突出症与前列腺素E2的相关性研究[J]．贵阳中医学院报，2005，27(2)：25～28．
31. O'Donnell JL, O'Donnell AL.Prostaglandin E2 content in herniated lumbar disc disease [3].Spine, 1996,21(14): 1653～1656.
32．亓建洪，王俊勤，鲁玉来，等．影响椎间盘退变生物化学改变的因素[J]．中国矫形外科杂志．2002，9(4)：381～382．
33. Rannou F, Corvol MT, Hudry C, et al. Sensitivity of annulus fibrosus cells to interleuikin 1β.Comparison with articular chondrocytes [J].Spine, 2000, 25(1): 17～23.
34. Burke JG, Waston RW, McCormack D, et al. lntervertebral discs which cause low back pain secrete high levels of proinflammatory mediators [J].J Bone Joint Surg Br,2002,84(2): 196～201.
35. Kanemoto M, Hukuda S, Komiya Y, et al. Immunohistochemical study of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 human intervertebral discs [J] .Spine, 1996, 21(1):1～8.
36. Liu J,Roughley PJ.Mort JS. Identification of human intervertebral disc stromelysin and its involvement in matrix degradation. J Orthop Res, 1991,9(4):568～575.
37. Chelberg MK,Banks GM,Geiger DF, et al. Identification of heterogeneous cell populations in normal human intervertebral disc. J Anat, 1995; 186(1):43～53.
38. Sakuma M, Fujii N, Takahashi T, et al .Effect of chondroitinase ABC on matrix metalloproteinases and inflammatory mediators produced by intervertebral disc of rabbit in vitro[J].Spine,2002,27(6):576～580.
39. Gruber HE, Hanley EN Jr. Analysis of aging and degeneration of the human intervertebral disc. Comparison of surgical specimens with normal controls[J].Spine, 1998,23(7):751～757.
40. Kang JD, Stefanovic-Racic M, Mclntyre LA, et al.Toward a Biochemical Understanding of human intervertebral disc degeneration and herniation.Spine, 1997,22(10):1065-1073.
41．戴力扬，等．中国临床应用解剖学杂志．1989，7：117．
42. Kuga N, Kawabuchi M. Histology of intervertebral disc protrusion: an experimental study using an aged rat model. Spine.2001,26(17):379～84.
43. van Deursen DL, Snijders CJ, Kingma I et al. In vitro torsion-induced stress distribution changes in porcine intervertebral discs. Spine 2001,26(23):2552～2586.
44．娄明武，褚丽娟，王英久，等．腰椎间盘的生物力学研究．1999，33(10)：713～715．
45. Farfan HF, Huberdeau RM, Dubow HI. The biomechanical study on the lumbar intervertebral discs in 182 cadavers. J Bone Joint Surg Am. 1972,54(3):492～510.
46. Lotz JC, Chin JR. lntervertebral disc cell death is dependent on the magnitude and duration of spinal loading [J].Spine,2000,25(12): 1477～1483.
47. Chiu EJ, Newitt DC, Segal MR et al. Magnetic resonance imaging measurement of relaxation and water diffusion in the human lumbar intervertebral disc under compression in vitro. Spine 2001,26(19):437～444.
48. Elfervig MK, Minchew JT, Francke E.IL-1 beta sensitizes intervertebral disc annulus cells to fluid-induced shear stress. J Cell Biochem.2001,82(2):290～298.
49．彭宝淦，贾连顺，施杞，等．软骨终板钙化在椎间盘退变过程中的作用机理．中国矫形外科杂志．2000，7(2)：147-150．
50. Kerttula LI, Serlo WS, Tervonen OA et al. Post-traumatic findings of the spine after earlier vertebral fracture in young patients: clinical and MRI study. Spine 2000, 25(9): 1104～1108.
51．陈立，詹红生，应航，等．长时间异常应力负荷下兔颈椎间盘的组织病理学观察．中国骨伤，2003，16(6)：374～375．
52. Kazarian LE. Creep characteristics of the human spinal column. Orthop Clin North Am, 1975, 6(1):3～18.
53．施杞，彭宝淦，贾连顺．椎体骨赘形成机理的实验研究．中国矫形外科杂志，1997，4(5)，397～398．