软骨终板的形态与椎间盘退变的关系

软骨终板位于椎体上、下表面与椎间盘的纤维环和髓核之间 ,刘润田〔1〕等认为是椎间盘的一个组成部分 ,另一些学者〔2〕认为椎体上、下表面的皮质外层。软骨终板和纤维环一起将胶状的髓核密封 ,使椎间盘形成一个自行限制的密闭容器 ,起缓冲外力的作用。若软骨终板破裂 ,髓核会通过其破裂处突入椎体骨质内形成许莫结节 ( Schmorl) ;或向后突入椎管内形成椎间盘突出。本文就软骨终板的形态和功能作一综述 ,旨在为椎间盘退变的进一步研究和人工椎间盘置换术等临床应用提供解剖学依据。椎间盘是人体最大的无血运组织 ,其营养途径主要有 :( 1 )…     

软骨终板与椎间盘退变的相关性研究进展

椎体软骨终板(vertebral endplate)为椎体上下缘表面的一层薄的透明软骨,其不仅同椎体的纵向生长密切相关,而且椎体软骨终板通路是椎间盘营养供应的主要途径,对维持脊柱的正常生理功能具有非常重要的作用[1].当椎间盘发生病理变化时,椎体软骨终板必然会发生相应的变化.现就软骨终板的结构生理功能及其与椎间盘退变的关系做一综述.     

转化生长因子β1注射退变椎间盘内软骨终板的组织形态变化

背景：椎间失稳能导致软骨终板的退变,是椎间盘退变发病机制中的基础环节。 目的：观察退变椎间盘内注射转化生长因子β1后,椎间盘软骨终板的组织形态学变化。 方法：将日本大耳白兔随机分为对照组、预防组和治疗组。所有兔均建立L5~6,L6~7椎间失稳模型。预防组在完成椎间失稳建模后立即于损伤侧L5~6,L6~7椎间盘内注射转化生长因子β1,治疗组于椎间失稳建模后3个月行相同方法注射转化生长因子β1。 结果与结论：建模后3,6个月,预防组较对照组软骨终板软骨细胞分布均匀,潮线清晰。Mankin评分降低(P < 0.05)。建模后第6个月治疗组较对照组软骨终板表层光滑,细胞排列均匀,潮线清晰,染色均匀,Mankin评分降低(P < 0.05)。结果证实,在兔椎间盘内注射转化生长因子β1可延缓椎间盘软骨终板的退变。     

软骨终板干细胞动物体内成骨/软骨的初步研究

目的观察软骨终板干细胞在动物体内成骨/软骨的能力。方法临床获取腰椎退变椎间盘软骨终板,采用琼脂糖筛选软骨终板干细胞后进行传代扩增,扩增后的软骨终板干细胞与羟基磷灰石复合后植入裸鼠皮下,7周后处死裸鼠取出复合物,分别进行特殊染色和免疫组化染色分析。同时,将扩增的干细胞注入兔子退变椎间盘中,16周后行MRI检测,观察退变椎间盘修复情况。结果软骨终板干细胞羟基磷灰石复合物切片经甲苯胺蓝染色后有异染性,提示有软骨基质形成;同时Mallory染色显示羟基磷灰石空隙中有蓝染存在,说明有成熟的骨基质形成。免疫组织化学结果提示,所形成的基质主要为Ⅰ型和Ⅹ型胶原,同时有少量Ⅱ型胶原表达。MRI结果提示植入退变椎间盘的终板干细胞在动物体内可以分化为类软骨样细胞,从而修复退变椎间盘。结论软骨终板干细胞可以在动物体内向成骨/软骨方向分化。     

消融髓核成形术中消融时间与椎间盘内压变化关系的实验研究

目的：研究消融髓核成形术中消融时间与椎间盘内压变化之间的量效关系，并观察消融后椎间盘髓核、终板形态学改变，探讨最佳的消融时间，为临床应用提供参考。 方法:选择2月龄的小型猪6只，平均体重22.5 kg，雌雄不拘，选取L1－S1共6个椎间隙进行消融，按消融时间的长短分10个不同时段测定消融后椎间盘内压，找出消融时间／椎间盘内压变化曲线。于不同消融时段随机从动物活体取出单个完整椎间盘，对髓核及终板进行HE染色，在普通光学显微镜下观察形态学改变。结果:实验动物正常椎间盘内压为（24.45±1.04） mmHg，椎间盘内压力符合正态分布，P>0.05。椎间盘内压随消融时间延长而逐渐降低，消融70 s后椎间盘内压达到平衡，70 s后椎间盘内压变化无统计学意义。病理显示消融后髓核组织出现空洞，消融至120 s时软骨终板完整，未见明显损伤。结论:椎间盘内压测量可以作为消融髓核成形术中椎间盘内压变化的监测手段，椎间盘内压变化与消融时间存在较明显的量效关系。消融70 s时椎间盘内压达到平台期，超过70 s后椎间盘内压的减少不再明显，消融区域未见扩大，软骨终板未见明显损伤。     

骨保护素基因敲除小鼠腰椎间盘退变与腰椎骨质疏松

背景：骨保护素基因敲除小鼠已被证明会表现出明显的骨质疏松及骨关节炎表型。 目的：观察骨保护素基因敲除小鼠随年龄增长腰椎间盘退变和骨质疏松的动态变化关系。 方法：分别取出生后4,8,12周的骨保护素基因敲除纯合子小鼠及正常对照组小鼠的L3椎体和L4/5椎间盘,运用Micro-CT检测L3椎体松质骨微结构指标;用苏木精-伊红染色法观察L4/5椎间盘形态学,测量椎间盘及软骨终板高度。 结果与结论：骨保护素基因敲除纯合子小鼠组L3椎体骨小梁数量、骨小梁厚度、骨体积分数较正常组均明显下降(P < 0.05),而骨小梁分离度、结构模型指数较正常小鼠增高(P < 0.05)。8周及12周的骨保护素基因敲除纯合子小鼠的L4/5椎间盘软骨终板出现退变征象,软骨终板排列不规则,并有骨髓腔组织进入软骨终板及外层纤维环。提示骨保护素基因在维持椎间盘正常的结构和功能方面起到重要作用,骨保护素基因缺失后可导致椎间盘退变和椎体骨质疏松。     

腰椎间盘退变对软骨终板生物力学特性影响的有限元分析

目的　研究腰椎终板不同位点的压应力分布规律,分析腰椎间盘退变对软骨终板压应力的影响。 方法　选取一青壮年男性新鲜尸体的腰椎运动节段标本,螺旋CT机对腰椎运动节段进行连续CT扫描,利用有限元分析方法,建立L4/5运动节段有限元分析模型,在此基础上建立椎间盘退变模型。模拟椎间盘正常状态和椎间盘退变状态,在L4、L5椎体终板上选择具有代表性的结点,分别代表椎体终板正中部、左右侧边缘、后中部和前中部,对上下软骨终板压应力分布进行有限元分析。 结果　椎间盘退变组较正常组的终板压应力均显著增大,上下终板在轴向加载、前屈、后伸、左旋和右旋加载时椎间盘退变组较正常状态时应力分布均显著增大,具有统计学意义（P<0.05）。 结论　腰椎椎间盘退变因素对终板的应力分布有明显影响, 随着椎间盘退变,椎间盘软骨终板应力显著增大。     

六味地黄丸含药血清对软骨终板蛋白多糖的影响

背景：软骨终板的结构完整性关系着其生理功能的正常发挥,进而影响整个椎间盘的生理、病理状态;蛋白多糖是软骨终板的主要组分。 目的：观察六味地黄丸含药血清对肿瘤坏死因子α致伤兔软骨终板蛋白多糖含量的影响。 方法：将12只新西兰白兔带终板的24个T12~L2椎间盘随机等分为对照第1,14天组、肿瘤坏死因子α组、肿瘤坏死因子α+中药血清组。后2组培养液中分别含5 μg/L肿瘤坏死因子α,5 μg/L肿瘤坏死因子α和体积分数10%六味地黄丸血清,培养14 d后观察。 结果与结论：随培养时间的延长,软骨终板细胞数量减少、细胞形态变化明显,细胞外基质中胶原水平减少,加入肿瘤坏死因子α,胶原成分下降更快,并出现大量裂隙,含药血清可部分延缓这一过程;随着培养时间延长,软骨终板超微结逐渐损伤,肿瘤坏死因子α可加重损伤,含药血清可部分抑制这种损伤;随着培养时间的延长,各组椎间盘软骨终板的糖胺多糖总量与硫酸软骨素、硫酸角质素和透明质酸水平均降低;肿瘤坏死因子α加速这种结果,而含药血清可延缓生化成分水平的下降。提示六味地黄丸可通过保护软骨终板超微结构,稳定糖胺多糖总量及其各成分水平,对椎间盘软骨终板具有保护作用。     

椎间盘突出患者椎间盘Fas基因的表达

背景：临床中发现腰椎间盘突出症常在一个家族中多人甚至全部发病,而且发病的部位、原因、症状基本一致,这表明基因在该种病症中扮演着重要的角色。 目的：分析家族性腰椎椎间盘突出症患者椎间盘内Fas凋亡基因表达的特点。 方法：用半定量RT-PCR方法检测15例家族性腰椎椎间盘突出患者、21例普通椎间盘突出患者、5例新鲜尸体椎间盘的软骨终板和髓核组织中Fas基因的表达情况。 结果与结论：家族性椎间盘突出与普通椎间盘突出患者终板内Fas基因的表达均高于新鲜尸体椎间盘终板内Fas基因的表达,差异有显著性意义(P < 0.05),家族性椎间盘突出与普通椎间盘突出患者终板内Fas基因的表达差异无显著性意义(P > 0.05)。家族性椎间盘突出患者髓核内Fas基因表达与普通椎间盘突出患者、新鲜尸体髓核内Fas基因表达相比较,差异无显著性意义(P > 0.05)。结果可见家族性椎间盘终板中Fas基因的表达增加可能是继发性的,可以通过阻止终板退变来达到阻止椎间盘退变的目的。     

椎间融合与双侧经椎弓根经椎间盘螺钉置入后腰椎生物力学的有限元分析

背景：腰椎经椎弓根经椎间盘螺钉是一种新的微创脊柱内固定技术，与传统双侧椎弓根螺钉固定相比，单侧只需1枚螺钉固定1个节段，具有经济微创、操作便捷等优点。但目前探讨应用双侧经椎弓根经椎间盘螺钉联合改良经椎间孔入路腰椎椎间融合(transforaminal lumbar interbody fusion,TLIF)术式的研究仍很少见。目的：通过建立改良TLIF无内固定(cage alone)、改良TLIF联合双侧椎弓根螺钉内固定(cage+BPS)和改良TLIF联合双侧经椎弓根经椎间盘螺钉内固定(cage+BTPTDS) 3种有限元模型，评估改良TILF联合不同内固定对椎间融合器(cage)、内固定、椎间盘、下终板的应力分布及腰椎活动度的影响。方法：采集成人腰椎薄层CT扫描图像，通过Mimics、Geomagic和SolidWorks软件建立3种有限元模型：cage alone模型、cage+BPS模型和cage+BTPTDS模型。采用ANSYS Workbench模拟施加人体前屈、后伸、左侧弯、右侧弯、左侧旋转、右侧旋转6种不同运动载荷，计算3种模型cage及内固定、下终板、椎间盘应力分布...     

Inhibition of vertebral endplate perfusion results in decreased intervertebral disc intranuclear diffusive transport

Impaired nutrition of the intervertebral disc has been hypothesized to be one of the causes of disc degeneration. However, no causal relationship between decreased endplate perfusion and limited nutrient transport has been demonstrated to support this pathogenic mechanism. To determine the importance of endplate perfusion on solute diffusion into the nucleus pulposus and to show causality of endplate perfusion on intranuclear diffusion in large animal lumbar intervertebral discs, diffusive transport into ovine lumbar intervertebral discs was evaluated after inhibiting adjacent vertebral endplate perfusion. Partial perfusion blocks were created in vertebrae close and parallel to both endplates of lumbar discs of anaesthetized sheep. To assess diffusivity of small molecules through the endplate, N2O was introduced into the inhalation gas mixture and concentrations of intranuclear N2O were measured for 35 min thereafter. Post mortem, procion red was infused through the spinal vasculature and perfusion through the endplate was assessed by quantifying the density of dye-perfused endplate vascular buds in histology sections. Perfusion of the endplates overlying the nucleus pulposus was inhibited by almost 50% in the partially blocked discs relative to the control discs. There was also a nine-fold decreased transport rate of intranuclear N2O in partially blocked discs compared with control discs. The density of perfused endplate vascular buds correlated significantly to the amount of transported intranuclear N2O (r2 = 0.52, P = 0.008). The vertebral endplate was demonstrated to be the main route of intravascular solute transport into the nucleus pulposus of intervertebral discs, and inhibition of endplate perfusion can cause inhibited solute transport into the disc intranuclear tissue.     

Factors regulating viable cell density in the intervertebral disc: blood supply in relation to disc height

The intervertebral disc is an avascular tissue, maintained by a small population of cells that obtain nutrients mainly by diffusion from capillaries at the disc–vertebral body interface. Loss of this nutrient supply is thought to lead to disc degeneration, but how nutrient supply influences viable cell density is unclear. We investigated two factors that influence nutrient delivery to disc cells and hence cell viability: disc height and blood supply. We used bovine caudal discs as our model as these show a gradation in disc height. We found that although disc height varied twofold from the largest to the smallest disc studied, it had no significant effect on cell density, unlike the situation found in articular cartilage. The density of blood vessels supplying the discs was markedly greater for the largest disc than the smallest disc, as was the density of pores allowing capillary penetration through the bony endplate. Results indicate that changes in blood vessels in the vertebral bodies supplying the disc, as well as changes in endplate architecture appear to influence density of cells in intervertebral discs.     

Geometry of the Intervertebral Volume and Vertebral Endplates of the Human Spine

Replacement of a degenerated vertebral disc with an artificial intervertebral disc (AID) is currently possible, but poses problems, mainly in the force distribution through the vertebral column. Data on the intervertebral disc space geometry will provide a better fit of the prosthesis to the vertebrae, but current literature on vertebral disc geometry is very scarce or not suitable. In this study, existing CT-scans of 77 patients were analyzed to measure the intervertebral disc and vertebral endplate geometry of the lumbar spine. Ten adjacent points on both sides of the vertebrae (S1-superior to T12-inferior) and sagittal and transverse diameters were measured to describe the shape of the caudal and cranial vertebral planes of the vertebrae. It was found that the largest endplate depth is located in the middle or posterior regions of the vertebra, that there is a linear relationship between all inferior endplate depths and the endplate location (p < 0.0001) within the spinal column, and that the superior endplate depth increases with age by about 0.01 mm per year (p < 0.02). The wedge angle increases from T12-L1 to L5-S1. The results allow for improvement of the fit of intervertebral disc-prostheses to the vertebrae and optimized force transmission through the vertebral column.     

大鼠颈椎间盘老化及退变过程中髓核形态变化规律的实验研究

目的：研究颈椎间盘自然老化及退变过程中髓核软骨样细胞的来源和脊索性髓核向纤维软骨性髓核转化的规律及其与颈椎间盘退变的关系。方法：4周龄SD大鼠76只，随机分成两组。实验组40只大鼠通过截除前肢制备双后肢大鼠颈椎间盘退变的动物模型，按术后3、6、9、12个月4个时间段分组，每组10只；对照组36只大鼠未予处置，按实验开始后4、8、12、16个月分4组，每组9只。制备C4-5，C5-6和C6-7椎间盘中矢状面组织学切片，行HE、番红-O染色，研究观察不同老化及退变程度颈椎间盘髓核中软骨样细胞的起源和脊索性髓核向纤维软骨性髓核转化的规律。结果：随着颈椎间盘的不断老化，终板的软骨细胞向髓核迁移，脊索性髓核向心性皱缩并最终完全被纤维软骨性髓核取代，在此过程中，软骨终板的厚度逐渐变薄，进而出现缺损或断裂；在颈椎间盘退变的过程中，这一转化完成的更快、更早。结论：髓核中的软骨样细胞由终板的软骨细胞迁移而来，通过向心性的产生和沉积胶原纤维，脊索性髓核逐渐被纤维软骨性髓核替代，这一过程既是颈椎间盘成熟和老化的自然环节也可能是颈椎间盘退变的启动环节。     

Finite element modeling of the cervical spine: role of intervertebral disc under axial and eccentric loads

An anatomically accurate, three-dimensional, nonlinear finite element model of the human cervical spine was developed using computed tomography images and cryomicrotome sections. The detailed model included the cortical bone, cancellous core, endplate, lamina, pedicle, transverse processes and spinous processes of the vertebrae; the annulus fibrosus and nucleus pulposus of the intervertebral discs; the uncovertebral joints; the articular cartilage, the synovial fluid and synovial membrane of the facet joints; and the anterior and posterior longitudinal ligaments, interspinous ligaments, capsular ligaments and ligamentum flavum. The finite element model was validated with experimental results: force–displacement and localized strain responses of the vertebral body and lateral masses under pure compression, and varying eccentric anterior-compression and posterior-compression loading modes. This experimentally validated finite element model was used to study the biomechanics of the cervical spine intervertebral disc by quantifying the internal axial and shear forces resisted by the ventral, middle, and dorsal regions of the disc under the above axial and eccentric loading modes. Results indicated that higher axial forces (compared to shear forces) were transmitted through different regions of the disc under all loading modes. While the ventral region of the disc resisted higher variations in axial force, the dorsal region transmitted higher shear forces under all loading modes. These findings may offer an insight to better understand the biomechanical role of the human cervical spine intervertebral disc.     

Menopause causes vertebral endplate degeneration and decrease in nutrient diffusion to the intervertebral discs

The vasculature in the outer annulus supplies only the periphery of the disc so that nutrition to the bulk of the disc, including all the inner annulus and nucleus pulposus, is derived from the vertebral epiphyseal end arteries where nutrients diffuse across the cartilaginous endplate to reach the disc. In this regard the vertebral endplate plays an important role in disc nutrition. Compromise of diffusion of nutrients to the disc cells may play a large part in the progression or even initiation of disc degeneration. Increasing evidence suggests that estrogen deficiency also influence the severity of disc degeneration in post-menopausal females. Structural disorganization of the vertebral endplate occurs with disc degeneration, with the most common endplate changes observed clinically being Schmorl’s node. Schmorl’s node is more commonly seen in post-menopausal women than younger women. Osteosclerosis, osteonecrosis and fibrosis associated with Schmorl’s nodes can impede nutrient diffusion into the disc as well as removal of metabolites from the disc. We hypothesize that menopause negatively affects vertebral endplate quality and induces endplate degeneration. This endplate degeneration decreases nutrients diffusion from vertebral body into discs, and also impedes removal of metabolites, leads to further disc degeneration. To confirm our hypothesis, a cross-sectional post-contrast MRI study can be performed in pre-menopausal and post-menopausal women. If the hypothesis is confirmed, then low dose hormone replacement treatment may retard disc degeneration in post menopausal women and thereby limit the consequences associated with disc degeneration such as low back pain.