椎间盘退变与终板内微血管形态改变的相关性研究

目的:通过观测大白兔椎间盘退变过程中椎间盘终板内的血管形态以及血流量的改变,探讨终板内微血管的改变与椎间盘退变之间的相关性.方法:选用40只新西兰大白兔随机分为2组,通过切除造模组20只免腰椎棘间、棘上韧带及棘突、关节突,造成力学失稳状态诱导形成椎间盘退变模型.分别在术后4、8个月通过扫描电镜、血流激光多普勒仪测定椎体终板内的血管形态以及血流量.结果:在椎间盘退变过程中,椎间盘终板内的血管芽形态逐渐被破坏,微血管数量相应减少,终板内的血流量也明显减少,同时终板内血流量中心部位(靠近髓核区域)血流量多于终板内周围区域的血流量.结论:椎体终板内微血管的改变可能是椎间盘退变的促进因素.     

椎间盘退变与终板内微血管形态改变的相关性研究

目的：通过观测大白兔椎间盘退变过程中椎间盘终板内的血管形态以及血流量的改变，探讨终板内微血管的改变与椎间盘退变之间的相关性。方法：选用40只新西兰大白兔随机分为2组，通过切除造模组20只兔腰椎棘间、棘上韧带及棘突、关节突，造成力学失稳状态诱导形成椎间盘退变模型。分别在术后4、8个月通过扫描电镜、血流激光多普勒仪测定椎体终板内的血管形态以及血流量。结果：在椎间盘退变过程中，椎间盘终板内的血管芽形态逐渐被破坏，微血管数量相应减少，终板内的血流量也明显减少，同时终板内血流量中心部位(靠近髓核区域)血流量多于终板内周围区域的血流量。结论：椎体终板内微血管的改变可能是椎间盘退变的促进因素。     

实验性椎间盘退变的放射影像学与病理学观察

目的　研究椎间盘退变过程中 ,椎间盘退变的放射影像学与病理学改变。方法　选用 4 0只新西兰大白兔随机分为 2组 ,实验组切除兔腰椎间棘间、棘上韧带及棘突、关节突 ,造成力学失稳状态诱导形成椎间盘退变模型。术后一周、 3个月、 8个月时摄腰椎正、侧位X线片 ,观察腰椎影像学变化。第 3个月、 8个月时取腰椎间盘 ,进行组织检查 ,评定椎间盘退变的病理改变情况。结果　模型建立后 ,3个月、 8个月的X线片显现对照组无明显改变 ,实验组腰椎后突畸形 ,椎间隙狭窄 ,随着时间延长椎体软骨终板钙化更加明显。组织学观察发现 ,实验组随术后时间延长 ,髓核由椎间盘内脱出 ,并伴有椎间盘两侧软骨终板的纤维化即软骨终板发生退变。结论　椎体软骨终板的退变是椎间退变早期的主要表现方式。     

椎体终板形态与椎间盘营养的关系

椎体终板是椎间盘的主要组成部分。以往研究表明 ,椎体终板对维持椎间盘营养和保护椎间盘形态起到重要作用 ,保持椎体终板有效的抗压作用是可以减少椎间盘退变的力学因素 ;椎间盘是人体最大的无血管组织 ,终板途径做为椎间盘营养的主要途径 ,其营养椎间盘的血管通路的多少及范围也直接影响到椎间盘营养供应。1　椎间盘与椎体终板的解剖椎间盘是由椎体终板、纤维环及髓核三部分组成的 ,椎间盘在出生时包含许多微血管 ,成人时则变为人体最大无血管结构 ,然而仍保持活跃的代谢 ,是椎体海绵质主要渗透及弥散部位。椎体终板位于椎体的上、下面的…     

软骨终板钙化与椎间盘退变关系的实验研究

目的　研究椎体软骨终板钙化与椎间盘退变的关系。　方法　通过切除２０ 只兔颈椎棘上、棘间韧带及分离颈椎后旁两侧肌肉造成颈椎力学上的失稳而诱导了颈椎间盘退变动物模型。在形态学上评定颈椎间盘退变程度,测定不同退变程度椎间盘软骨终板钙化层与非钙化层厚度。　结果　软骨终板钙化层厚度与椎间盘退变程度呈高度正相关性（ｒ＝ ０－９２） 。　结论　软骨终板的钙化可能是椎间盘退变的启动和促进因素     

实验性椎间盘退变的放射影像学与病理学观察

目的 研究椎间盘退变过程中，椎间盘退变的放射影像学与病理学改变。方法 选用40只新西兰大白兔随机分为2组，实验组切除兔腰椎间棘间、棘上韧带及棘突、关节突，造成力学失稳状态诱导形成椎间盘退变模型。术后一周、3个月、8个月时摄腰椎正、侧位X线片，观察腰椎影像学变化。第3个月、8个月时取腰椎间盘，进行组织检查，评定椎间盘退变的病理改变情况。结果 模型建立后，3个月、8个月的X线片显现对照组无明显改变，实验组腰椎后突畸形，椎间隙狭窄，随着时间延长椎体软骨终板钙化更加明显。组织学观察发现，实验组随术后时间延长，髓核由椎间盘内脱出，并伴有椎间盘两侧软骨终板的纤维化即软骨终板发生退变。结论 椎体软骨终板的退变是椎间退变早期的主要表现方式。     

兔椎体软骨终板血管芽增龄性变化

目的 探讨不同年龄段兔椎体软骨终板内血管芽的形态变化与椎间盘退变的关系.方法 15只不同年龄段新西兰兔,2月龄5只,1年龄5只,3年龄5只,雌雄不限.X线观察终板有无钙化及椎体周围有无骨赘形成,组织学观察软骨终板和椎间盘的形态学变化,血管铸型后扫描电镜观察终板各部位血管的形态变化.按Miyamoto等分级标准将椎间盘分为1～5级,分别规定为1～5分.采用t检验,分别对2月龄组和1年龄组髓核区与内层纤维环区,2月龄组及1年龄组兔髓核区、内层纤维环区椎体终板内血管直径进行比较.结果 2月龄组终板无明显钙化、软骨终板结构良好、潮标清晰,髓核及纤维环结构饱满清晰;1年龄组终板轻度钙化,髓核皱缩,纤维环出现裂隙;3年龄组终板钙化明显,密度增高,并可见骨赘形成,髓核消失.随着年龄增加,终板内微血管逐渐减少,最终消失,软骨终板中心部位较周围部血管减少更为明显.组织学显示软骨终板出现钙化,软骨终板退变重于椎间盘;钙化的程度与椎间盘退变程度呈正相关.2月龄组髓核区与内层纤维环区椎体终板内血管直径比较,差异有统计学意义;2月龄组与1年龄组髓核区椎体终板内血管直径比较,差异有统计学意义.结论 随着兔年龄增加终板内血管逐渐减少,终板发生退变,其程度重于椎间盘,提示椎体终板内微血管的变化可能是椎间盘退变的重要促进因素.

Abstract：

Objective To observe the morphologic changes of of vascular buds in vertebral cartilage endplate in age-specific rabbits and also to investigate the correlation between the changes of vascular buds and interverbral disc degeneration. Methods There were 15 New Zealand white rabbits in our study,which include three groups, 2-week-old rabbits, 1-year-old rabbits and 3-year-old rabbits, and each groups had five rabbits. The X-ray radiograph, histology and scanning electron microscope were used to observe the changes of vertebral cartilage endplate. According to Miyamoto standard, the interverbral disc was graded 1-5, and scored 1-5 respectively. Results The changes of micro-vascular structure of vertebral cartilage endplate were observed during aging. Under the scanning electron microscope, the vascular structure degenerated gradually, and disappeared in the end. The blood vessels in the central region of the vertebral cartilage endplate reduced more obviously than those in periphery region. The severe degeneration was found in vertebral endplate, compared with intervertebral disc. The changes of vascular buds in rabbits vertebral cartilage endplate had positive correlation with the vertebral endplate calcification and the interbertebral disc degeneration. Conclusion Changes of vascular buds in vertebral endplate may accelerate intervertebral disc degeneration.     

椎体终板与椎间盘退变

椎间盘退变是导致下腰痛的常见原因,与之密切相关的椎体终板退变也逐渐受到重视.MRI的T1和T2加权像上,退变的椎体终板表现为终板与终板下骨相对于正常终板的信号改变,且与对应的椎间盘退变有较高的相关性.经椎体终板的弥散是椎间盘获得营养的主要途径,同时椎体终板又是脊柱运动单位中最容易受损伤的部位,轴向负荷可导致软骨终板、骨性终板及终板下骨小梁弯曲变形,软骨终板与骨性终板分离.这一系列的终板损伤和软骨终板钙化和骨化会妨碍椎间盘营养供应,导致椎间盘组织学退变.新近研究进一步表明椎体终板与椎间盘退变不仅在组织学上密切相关,而且在力学上也密不可分,椎板形状如曲率也与椎间盘退变和突出存在一定的关联.     

软骨终板钙化在椎间盘退变过程中的作用机理

目的：研究椎体软骨终板钙化在椎间盘退变过程中的作用。人新西兰兔随机分为造模与对照组２组,每组发３个月和８个月２个观察亚组。切作造模组动物颈棘上、棘间韧带及分离颈椎后旁两侧肌肉,造成颈椎力学上的失衡而诱导兔颈椎间盘退行性改变。在术后３个月和８个地分别处死,取颈椎间盘组织,行病理学检查在形态学上评定颈椎间盘退变程度,测定不同退变程度椎间盘软骨终板钙化层厚度。结果：退变程度较轻或基本正常的颈椎间盘,软骨     

Schmorl结节与椎间盘退变和腰痛相关性的研究进展

1927年,德国医生Schmorl第一次描述了Schmorl结节及其形成理论:由椎间盘的髓核组织经软骨终板的薄弱区疝入椎体内所形成的椎间盘改变.长期以来,经典的Schmorl结节定义至少包含两个部分:一是椎体软骨终板的破裂;二是髓核通过破裂的软骨终板突向软骨下松质骨内.但至今为止,Schmorl结节的发生因素、分布规律以及与椎间盘退变、腰痛的关系尚不明确.现将当前国内外关于Schmorl结节与椎间盘退变及腰痛相关性的研究进展综述如下.     

终板下椎体缺血诱导兔椎间盘退行性变模型的建立及终板中内皮素1的表达

目的通过终板下注射无水乙醇阻碍椎体-终板营养,建立一种新型兔腰椎椎间盘退行性变模型,并观察终板退行性变过程中内皮素1(ET-1)的表达情况。方法健康4月龄新西兰兔32只,随机分成4组,每组8只,选取L5,6椎体(对应L4/L5及L5/L6椎间盘)注射300μL无水乙醇,选取L4椎体(对应L3/L4椎间盘)注射磷酸盐缓冲液(PBS)作为实验对照,L7椎体(对应L6/L7椎间盘)未注入任何物质作为正常对照。其中1组造模后1个月提取软骨终板细胞,行免疫细胞化学染色检测ET-1表达;余3组分别于造模后1、3和5个月进行椎间盘X线和MRI检查,取椎间盘组织行HE染色观察形态学改变,免疫组织化学染色观察ET-1表达。结果注射无水乙醇后,随着时间进展,X线片显示椎间隙高度显著下降、椎间隙变窄、边缘骨赘增生,MRI T2WI显示椎间盘低信号;苏木精-伊红染色(HE)显示终板的生长板厚度变薄,终板结构破损,同时软骨终板细胞退化、直至消失,髓核中细胞发生转化(由空泡细胞转变为软骨样细胞,进而形成纤维软骨样细胞)造成髓核纤维化,纤维环结构排列紊乱、纤维化程度逐步加重;免疫组织化学染色显示,发生退行性变的终板组织内有ET-1表达,但随着退行性变加剧,ET-1表达强度下降;提取的退行性变软骨终板细胞(造模后1个月)也显示细胞质内ET-1强表达。结论通过注射无水乙醇阻碍椎体-终板营养途径可成功建立兔椎间盘退行性变模型,终板退行性变过程中伴随ET-1的表达。     

Intervertebral Disc Degeneration Is Associated With Aberrant Endplate Remodeling and Reduced Small Molecule Transport

The intervertebral disc is the largest avascular structure in the body, and cells within the disc rely on diffusive transport via vasculature located within the vertebral endplate to receive nutrients, eliminate waste products, and maintain disc health. However, the mechanisms by which small molecule transport into the disc occurs in vivo and how these parameters change with disc degeneration remain understudied. Here, we utilize an in vivo rabbit puncture disc degeneration model to study these interactions and provide evidence that remodeling of the endplate adjacent to the disc occurs concomitant with degeneration. Our results identify significant increases in endplate bone volume fraction, increases in microscale stiffness of the soft tissue interfaces between the disc and vertebral bone, and reductions in endplate vascularity and small molecule transport into the disc as a function of degenerative state. A neural network model identified changes in diffusion into the disc as the most significant predictor of disc degeneration. These findings support the critical role of trans-endplate transport in disease progression and will improve patient selection to direct appropriate surgical intervention and inform new therapeutic approaches to improve disc health. © 2020 American Society for Bone and Mineral Research. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.     

Localization of cathepsins D, K, and L in degenerated human intervertebral discs.

STUDY DESIGN: Localization of cathepsins D, K, and L in degenerated intervertebral discs was examined by immunohistochemistry. OBJECTIVES: To determine the involvement of cathepsins in the pathomechanism of intervertebral disc degeneration by monitoring the immunolocalization of cathepsins in degenerated intervertebral disc tissue. SUMMARY OF BACKGROUND DATA: Cathepsins D, K, and L are enzymes that contribute to the matrix destruction seen in the articular cartilage affected by osteoarthritis and rheumatoid arthritis. However, little is known about the contribution of these cathepsins to intervertebral disc degeneration. METHODS: Paraffin-embedded sections of degenerated intervertebral disc tissue collected at the time of surgery (13 discs from 12 patients) were immunohistochemically stained with antibodies for cathepsins D, K, and L. For further characterization of the stained cells, immunohistochemical detection of CD68 and TRAP staining were performed. RESULTS: Hematoxylin and eosin staining revealed obvious signs of degeneration in all sections. Cathepsins D and L were immunolocalized in disc fibrochondrocytes at various sites exhibiting degeneration. Cathepsins K were found in tartrate-resistant acid phosphatase-positive multinucleated cells, in particular near the cleft within the cartilaginous endplate. However, few cells were positive for these cathepsins in anulus fibrosus that maintained the lamellar structure of collagen fibers. CONCLUSIONS: Marked expression of cathepsins D and L was observed at the site of degeneration. Cathepsins D and K localized in tartrate-resistant acid phosphatase-positive multinucleated cells existed at the cleft between the cartilaginous endplate and vertebral body. The site-specific localization of these cathepsins suggests the association of these proteinases with endplate separation and disorganization of the anulus fibrosus in degenerative spinal disorders.     

Association and histological characteristics of endplate injury and intervertebral disc degeneration in a rat model

IntroductionThe purpose of this study was to construct a rat caudal vertebral body fracture model and to analyze the association and histological characteristics of vertebral body fracture with endplate injury and adjacent intervertebral disc degeneration.Materials and methodsThis study included 144 clean-grade male Sprague-Dawley rats, which were randomly divided into a control, middle vertebral body injury (MI), and endplate injury (EI) groups. A vertebral body fracture with or without endplate injury was developed by either drilling a hole in the middle of a rat caudal vertebral body to create a fracture with an intact endplate or drilling a hole in the vertebral body near the intervertebral disc to create a vertebral body fracture with endplate injury. The histological differences in the adjacent intervertebral discs of vertebral body fractures with or without endplate injury were detected using imaging, non-specific histological staining, immunohistochemistry and TUNEL assay.ResultsImaging results revealed that the EI group showed a significant decrease in intervertebral space height and intervertebral disc T2 signal over time. Non-specific histological staining revealed that in the EI group, the intervertebral disc was degenerative. Immunohistochemistry indicated that Aggrecan and Collagen-II were decreased and inflammatory factors were increased in the EI group. The TUNEL detection found that apoptosis was significantly increased in the EI group as compared with the MI and control groups.ConclusionIn rat caudal vertebral body fractures, a fracture with endplate injury is more likely to induce or accelerate degeneration of adjacent intervertebral discs.     

The effect of nucleotomy on lumbar spine mechanics in compression and shear loading.

STUDY DESIGN: An in vitro biomechanical investigation on human cadaveric specimens was conducted before and after nucleotomy. Endplate and vertebral body deformation patterns were measured under compression and shear loading, in addition to kinematics and disc pressure. OBJECTIVE: The working hypotheses of this study were that in compression, nucleotomy results in an altered deformation pattern of the endplate and that in shear, nucleotomy does not result in an altered endplate deformation pattern or disc pressure. SUMMARY OF BACKGROUND DATA: The pressure distributions within the intervertebral disc have been studied in compression loading but not in shear loading. Severe degeneration and surgical nucleotomy result in small nuclear pressure and altered loading distribution in compression. The effect of these changes on the vertebral endplate and the response under shear loads are not well understood. METHODS: Five L3-L4 and two L4-L5 functional spinal units were tested under compression and shear loading, intact and after nucleotomy. Vertebral body deformations, intradiscal pressure, and intervertebral kinematics were measured. A series of compression-type (maximum 1000 N) and shear-type (maximum 500 N) loads were applied. RESULTS: With nucleotomy, the disc pressure and the endplate strains decreased under compression, but the vertebral rim strains did not change. In shear, the vertebral rim and endplate strains did not change with nucleotomy. Disc pressure was lower in shear than in compression. CONCLUSION: Nucleotomy resulted in decreased disc pressure, decreased endplate deformation, and modified loading patterns onto the inferior vertebra in compression loading. However, nucleotomy did not appreciably affect the behavior of the disc in shear loading.     

The relationship between apoptosis of endplate chondrocytes and aging and degeneration of the intervertebral disc.

STUDY DESIGN: Apoptosis in cervical intervertebral disc cells and cartilaginous endplate cells was examined by the nick end labeling (TUNEL) technique during the process of natural aging and in a mouse experimental spondylosis model. OBJECTIVES: To determine the role of apoptosis in aging and degeneration of intervertebral discs by monitoring chronologic changes in the quantity and localization of apoptotic cells. SUMMARY OF BACKGROUND DATA: Apoptosis occurs within human intervertebral discs, but little is known about the pathologic significance of this process. On the other hand, the cartilaginous endplate is known to decrease in thickness and to disappear with aging and degeneration. The cause of this age-related change remains unclear. METHODS: A mouse spondylosis model was prepared via surgical resection of the posterior spinal element in 12 mice to examine the experimentally induced spondylosis process. Eighteen naturally aged mice were also used to examine the influence of aging. Paraffin-embedded midsagittal sections of the cervical spine were obtained 2, 3, 6, and 12 months after surgery in the spondylosis model and in the age-matched naturally aged mice, as well as in 4-week-old and 18-month-old naturally aged mice. Sections were stained with hematoxylin and eosin, safranin-O, and the TUNEL procedure. The number of apoptotic cells and vital cells were counted in the cartilaginous endplate of the intervertebral disc excluding the growth cartilage, and the degree of disappearance of the cartilaginous endplate was evaluated. RESULTS: Apoptosis, particularly noticeable in the cartilaginous endplate, increased with age and resulted in a marked decrease in cell density. Subsequently, the structure of the cartilaginous endplate began to disappear. Apoptosis was more evident and the structure of the cartilaginous endplate began to disappear more rapidly in the surgically treated group than in the naturally aged group. CONCLUSIONS: TUNEL-positive cells in the cartilaginous endplate increased with age, with destruction of the cartilaginous endplate after apoptosis (TUNEL-positive cell death). The application of the spondylosis model increased the incidence of apoptosis preceding the development of spondylosis. This suggests that apoptosis plays a role in the age-related changes seen in the cartilaginous endplate of the intervertebral disc and in the experimentally induced spondylosis process.     

颈椎终板软骨细胞凋亡的检测及相关意义

目的检测颈椎终板软骨细胞的细胞凋亡指数,探讨其在椎间盘退变中可能的作用机制。方法颈椎间盘终板及髓核取自我院行颈椎前路手术的35例颈椎椎间盘退变患者（退变组）和19例颈椎外伤患者（外伤组）。光镜观察退变组和外伤组终板和髓核的细胞密度,TUNEL法检测两组终板软骨细胞和髓核细胞的细胞凋亡指数,咔唑分光光度法比较两组髓核蛋白多糖含量。结果退变组终板细胞密度较外伤组减少（P〈0.05）,TUNEL染色显示退变组终板细胞凋亡指数为（34.6±16.1）%,外伤组为（20.1±9.3）%,两组间比较差异有统计学意义（P〈0.05）。Pearson相关分析显示,颈椎终板TUNEL染色阳性细胞率与终板细胞密度、髓核蛋白多糖含量之间呈负相关（r=—0.805,P=0.001;r=—0.677,P=0.023）,与髓核TUNEL阳性细胞率之间呈正相关（r=0.758,P=0.003）。结论颈椎退变终板软骨细胞凋亡率较高,推测在椎间盘退变过程中可能发挥重要作用;软骨细胞凋亡可能与髓核细胞凋亡增加、终板细胞密度与髓核蛋白多糖含量降低密切相关。     

Morphology of the human vertebral endplate

It is presumed that poor intervertebral disc cell nutrition is a contributing factor in degeneration, and is exacerbated by vertebral endplate sclerosis. Yet, quantitative relationships between endplate morphology and degeneration are unavailable. We investigated how endplate bone microstructure relates to indices of disc degeneration, such as morphologic grade, proteoglycan content, and cell density. Intervertebral core samples [n = 96, 14 subjects, L1–L5 level, ages 35–85 (64 ± 16 years), degeneration grade 1 (n = 4), grade 2 (n = 32), grade 3 (n = 44), grade 4 (n = 10), grade 5 (n = 6)] that included subchondral bone, cartilage endplate, and adjacent nucleus were harvested from human cadaveric lumbar spines. The morphology of the vertebral endplate was analyzed using µCT and the adjacent nucleus tissue was collected for biochemical and cellular analyses. Relationships between vertebral endplate morphology and adjacent disc degeneration were analyzed. Contrary to the prevailing notion, vertebral endplate porosity increased between 50% and 130% and trabecular thickness decreased by between 20% and 50% with advancing disc degeneration (p < 0.05). We also observed that nucleus cell density increased (R² = 0.33, p < 0.05) and proteoglycan content decreased (R² = 0.47, p < 0.05) as the endplate became more porous. Our data suggest that endplate sclerosis is not a fundamental factor contributing to disc degeneration. Rather, the opposite was observed in our samples, as the endplate became progressively more porous with age and degeneration. Since ischemic disc cell behavior is commonly associated with degenerative change, this may be related to other factors such as the quality of vertebral capillaries, as opposed to decreased permeability of intervening tissues. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:280–287, 2012     

基于腰椎间盘退变的脊柱稳定性改变的MRI研究进展

腰椎间盘是位于两个相邻椎体之间的圆盘状纤维软骨,是维持脊柱稳定性的重要解剖结构。目前,维持脊柱稳定性的解剖结构分为被动亚系、主动亚系和神经控制亚系,称为"三亚系模型",腰椎间盘退变(intervertebral disc degeneration,IVDD)会引起该模型其它组织的病理学改变,且彼此相互作用导致脊柱稳定性下降,是下腰痛最常见的原因。IVDD患者常伴有椎小关节及韧带的退变、邻近椎体Modic改变、椎体血流量减少、椎旁肌肉脂肪浸润增加、神经轴向牵拉损伤的代偿性减少等。磁共振成像(magnetic resonance imaging,MRI)是评估脊柱稳定性首选的影像学方法,常规MRI能完整显示IVDD患者三亚系模型相关组织形态学变化,MRI功能成像能定量分析其病理生理学变化的程度。本文综述IVDD患者腰椎间盘、椎小关节、韧带、椎体、肌肉、神经的MRI形态学及定量值变化,阐述IVDD引起脊柱稳定性改变的相关机制,旨在为下腰痛患者的精准诊疗提供更全面的信息。