椎间盘退变模型研究进展

椎间盘退变的生物学机制尚不明确,构建椎闯盘退变模型是研究基础和关键.近年来国内外报道的新型椎间盘退变模型分为体外和体内培养模型两大类.体外模型包括椎间盘细胞模型和椎间盘组织块模型,多用于细胞生物学行为方面的研究,适用面较广,但培养要求较高,模拟体内环境有局限.体内模型有机械力学模型、外伤模型、酶化学模型、缺血模型、吸烟模型等,多用于采取特定干预措施的椎间盘退变模型的研究,适用面较窄,但干预技术较易实现.该文就近年来新型椎间盘退变模型的研究进展及各种模型的优缺点作一综述.     

Biologic modification of animal models of intervertebral disc degeneration

Intervertebral disc degeneration is a chronic process that can become manifest in clinical disorders such as idiopathic low back pain, sciatica, disc herniation, spinal stenosis, and myelopathy. The limited available treatment options (including discectomy and spinal fusion) for these and other disabling conditions that arise from intervertebral disc degeneration are highly invasive, achieve limited success, and only address acute symptoms while doing nothing to halt the process of degeneration. Although the precise pathophysiology of intervertebral disc degeneration has yet to be clearly delineated, the progressive decline in aggrecan, the primary proteoglycan of the nucleus pulposus, appears to be a final common pathway. Animal models as well as in vitro studies of the process of disc degeneration have yielded many potentially useful targets for the reversal of disc degeneration. One current research trend is the use of established animal models of disc degeneration to study the role of therapeutic modalities in reversing the process of degeneration, often with use of the delivery of genes or gene products that influence the anabolic and catabolic pathways of the disc. This article reviews the ability of gene-product delivery systems and gene therapy to alter biologic processes in animal models of disc degeneration and examines future trends in this field.     

Imaging intervertebral disc degeneration

Magnetic resonance imaging provides excellent anatomic detail of spinal tissues, but fails to provide the type of information that permits a definitive diagnosis in many patients with back pain. New imaging strategies that can be applied to the study of intervertebral disc degeneration include diffusion-weighted imaging, magnetic resonance imaging, diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, dynamic computed tomography and magnetic resonance imaging, and T2 relaxometry. With dynamic imaging, the relative motions of normal and degenerated lumbar motion segments can be evaluated noninvasively. With further evaluation of the technique, hypermobile segments may be distinguishable from those with normal relative motion. T2 measurements obtained by T2 relaxometry appear to have important advantages with regard to spinal imaging because this modality provides a continuous and objective measure of the content of free water in the disc, which decreases with aging and degeneration. Anatomic imaging of the spine is highly accurate in the evaluation of nonmechanical causes of back pain and less beneficial in the evaluation of back pain that is due to mechanical causes. The development of functional imaging strategies of the spine will likely improve the management of patients with back pain. This article outlines the current magnetic resonance imaging protocols for intervertebral disc degeneration, indicates deficiencies in current imaging, and describes functional imaging strategies for the spine that will likely improve the evaluation of patients with back pain. It also reviews recent published articles on magnetic resonance imaging and computed tomographic imaging of the spine and details the results of studies that have explored the future potential of spine imaging.     

椎间盘退变生物学治疗的研究进展

椎间盘退变所致的颈肩腰腿痛严重影响许多患者的生活及工作,目前的治疗方法主要侧重于缓解疼痛症状或神经受压症状,而无法阻止椎间盘退变的进程,导致疾病具有高复发率。近年来学者们开始广泛研究椎间盘退变的生物学治疗方法,即通过生物分子治疗、基因治疗、细胞治疗和组织工程等方法来修复和重塑椎间盘,以期从根本上解决椎间盘退变的问题,而上述方法大多处于动物实验或体外实验阶段,临床应用尚存在诸多挑战。     

腰椎椎间盘退行性变动物模型建立方法的研究进展

腰痛是目前全球首位致残疾病,给患者、家庭和社会造成极大的痛苦和沉重的负担.与增龄有关的椎间盘退行性变(IDD)是腰痛的最主要原因.随着工作与生活节奏的加快,IDD 呈现年轻化的趋势.建立符合IDD 规律、成功率高、可重复性好、操作简单、成本低且适合医学研究的IDD 动物模型,对明确腰椎IDD 的发生机制及开展防治工作具...     

椎间盘退行性变机制的研究进展

正椎间盘是脊柱中连接两个相邻椎体的纤维软骨盘,其中央部为富含弹性胶状物质的髓核,周围部是由多层纤维软骨环按同心圆排列而成的纤维环。椎间盘具有承受压力、缓冲震荡冲击、保护脊髓等作用。椎间盘退行性变(IDD)会引起一系列的临床症状,是引起下腰痛最主要的原因之一。一直以来,研究者们对引起IDD的过程不断进行观察与造模,目前也已有大量的IDD过程与机制的研究_([1-2])。总体而言,IDD是在椎间盘组织内髓核细胞数目减     

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.     

椎间盘退变相关的生物应力刺激

正椎间盘(intervertebral disc,IVD)位于相邻椎体之间,协助维持机体站立姿势及保证脊柱的活动性。椎间盘受到来自脊柱、椎旁肌肉等活动产生的动态负荷以及机体重力的静态负荷的共同作用~([1])。随着年龄的增长,椎间盘会发生退变,同时,举重、肥胖及振动等应力作用会加速椎间盘退变。作用在椎间盘上的应力负荷使椎间盘细胞受到压力性应力、牵张应力、静水压、渗透压以及剪切应力等各种应力刺激~([2]),值得注意的是,椎间盘内髓核、纤维环以及软骨终     

兔椎间盘退变模型的研究进展

人类多种脊柱疾病例如颈椎病、腰椎间盘突出症等疾病的根本病理变化是椎间盘退变,但其确切病因及病理生理机制目前仍不十分清楚.因此建立椎间盘退变实验动物模型,对深入研究其病因和发生机制是十分重要也是十分必要的.自从20世纪三十年代,Lob在损伤兔椎间盘纤维环后观察到椎间盘产生与人类椎间关节病变相似的变化,到目前为止研究者们根据不同的原理建立了多种兔椎间盘退变的模型.参考Lotz[1]对椎间盘退变模型的分类,我们可以把已建立的兔椎间盘退变模型分为:改变力学特性模型、破坏椎间盘组织模型和其他模型,综述如下.     

炎症因子与椎间盘退变

椎间盘退变是导致腰背痛的主要原因之一.研究证明,肿瘤坏死因子-α、白细胞介素-1β、前列腺素E2、环氧化酶-2、一氧化氮等炎症因子在椎间盘退变进程中起重要作用.它们主要通过引起炎症反应、诱导细胞凋亡等途径促进椎间盘退变,同时各种炎症因子之间还可相互影响.针对性地阻断退变椎间盘中炎症因子的作用途径,抑制其引起的炎症反应,减少椎间盘细胞凋亡,对于延缓椎间盘退变进程,减轻患者临床症状具有重要意义.     

炎性因子与椎间盘退变

椎间盘退行性变是腰腿痛的重要原因之一,其特征性改变是髓核中蛋白多糖特别是聚合体含量下降、胶原类型的改变及伴随的水分的丢失。目前,椎间盘退变的原因尚不完全清楚,白介素(IL)、肿瘤坏死因子-α(TNF -α)等炎性细胞因子(简称炎性因子)具有促进椎间盘蛋白多糖降解和抑制其合成,参与椎间盘炎症反应等作用,极可能在椎间盘退变及其继发性疾病发病机制中起重要的作用。1　椎间盘中的炎性因子及其来源和影响因素体内检测到的众多炎性因子中,IL - 1、IL - 6、IL - 8、IL - 10、TNF -α、干扰素-γ(IFN -γ)及集落刺激因子(GM -CSF)等…     

椎间盘退变目的基因研究

椎间盘退变基因治疗旨在经转基因方法维持正常椎间盘细胞种群表型和数量,增强细胞合成蛋白聚糖、Ⅱ型胶原能力,从而延缓和逆转椎间盘退变.许多研究表明目的基因通过载体转染退变椎间盘髓核、纤维环细胞,能恢复细胞的生理功能.椎间盘退变基因治疗涉及目的基因、载体、靶细胞、转染方法和基因表达调控,该文就椎间盘退变基因治疗的目的基因和基...     

微小RNA在椎间盘退变中的作用

下腰背部痛是一种发达国家及发展中国家常见的慢性疾病,其常归因于椎间盘退变。椎间盘退变与细胞凋亡,细胞外基质破坏,细胞增殖和炎症反应密切相关。目前,没有针对椎间盘退变的病理生理学的临床疗法。microRNA(miRNA)是一类小的非编码RNA分子,在转录后水平上调节基因表达。miRNA不仅可以调节体内许多正常的生理过程,还可以在许多疾病(包括退行性椎间盘疾病)的发展中起着重要作用。多种miRNA在退变的椎间盘组织和细胞中差异表达。其中,一些miRNA已被证明与椎间盘退变过程中的多种病理过程有关,包括细胞凋亡,细胞外基质的降解,细胞增殖,炎症反应及软骨终板的退变。本综述将主要关注miRNA在椎间盘退变中的作用和潜在的临床治疗意义。     

ADAMTS在椎间盘退行性变中的作用

<正>椎间盘退行性变(IDD)是诸多脊柱退行性疾病的病理基础,尽管其发生机制仍没有完全清楚,但是普遍认为椎间盘细胞外基质(ECM)降解代谢的显著增加是重要原因之一。在过去10年中,通过利用人体样本与动物模型对椎间盘ECM降解的研究已经取得了巨大的进步,其中认为降解ECM(如聚蛋白聚糖)的关键酶——含血小板凝血酶敏感蛋白的解聚蛋白样金属蛋白酶(ADAMTS)家族在此过程中发挥了重要的作用~[1-2],因而ADAMTS家族     

Mechanical initiation of intervertebral disc degeneration

STUDY DESIGN: Mechanical testing of cadaveric lumbar motion segments. OBJECTIVES: To test the hypothesis that minor damage to a vertebral body can lead to progressive disruption of the adjacent intervertebral disc. SUMMARY OF BACKGROUND DATA: Disc degeneration involves gross structural disruption as well as cell-mediated changes in matrix composition, but there is little evidence concerning which comes first. Comparatively minor damage to a vertebral body is known to decompress the adjacent discs, and this may adversely affect both structure and cell function in the disc. METHODS: In this study, 38 cadaveric lumbar motion segments (mean age, 51 years) were subjected to complex mechanical loading to simulate typical activities in vivo while the distribution of compressive stress in the disc matrix was measured using a pressure transducer mounted in a needle 1.3 mm in diameter. "Stress profiles" were repeated after a controlled compressive overload injury had reduced motion segment height by approximately 1%. Moderate repetitive loading, appropriate for the simulation of light manual labor, then was applied to the damaged specimens for approximately 4 hours, and stress profilometry was repeated a third time. Discs then were sectioned and photographed. RESULTS: Endplate damage reduced pressure in the adjacent nucleus pulposus by 25% +/- 27% and generated peaks of compressive stress in the anulus, usually posteriorly to the nucleus. Discs 50 to 70 years of age were affected the most. Repetitive loading further decompressed the nucleus and intensified stress concentrations in the anulus, especially in simulated lordotic postures. Sagittal plane sections of 15 of the discs showed an inwardly collapsing anulus in 9 discs, extreme outward bulging of the anulus in 11 discs, and complete radial fissures in 2 discs, 1 of which allowed posterior migration of nucleus pulposus. Comparisons with the results from tissue culture experiments indicated that the observed changes in matrix compressive stress would inhibit disc cell metabolism throughout the disc, and could lead to progressive deterioration of the matrix. CONCLUSIONS: Minor damage to a vertebral body endplate leads to progressive structural changes in the adjacent intervertebral discs.