颈椎间盘退变病因研究进展

目前关于颈椎间盘退变机制的研究报道很多 ,但其确切原因还不清楚 ,现将这方面的研究进展情况综述如下。1　颈椎间盘退变早期的影响因素1 1　软骨终板的改变软骨终板渗透是椎间盘营养供应的主要途径。年龄与应力等因素可引起软骨板内软骨细胞与基质成分的改变。成人软骨终板厚度约为 1mm ,随着年龄的增长而逐渐变薄 ,中年以后软骨终板可出现裂隙与破裂 ,且随年龄增长软骨终板血管数目减少 ,血流减慢淤积 ,蛋白多糖含量减少 ,终板逐渐钙化 ,出现不同程度的退变。这些改变不仅影响椎间盘细胞的营养供应 ,妨碍废物的排出 ,破坏基质代谢平衡 ,还…     

椎间盘软骨终板退变的研究进展

椎间盘的退变与多种因素相关,其中软骨终板作为椎间盘的组成部分,通过其渗透作用为椎间盘提供大部分营养,在维持椎间盘正常功能方面发挥重要作用。软骨终板退变作为椎间盘退变的始动因素近来受到广泛关注。软骨终板退变的具体机制尚不明确,但现有研究表明其退变与年龄、异常应力、局部炎症因子、软骨细胞凋亡、软骨基质退变等因素相关,深入研究各因素在终板退变过程中的具体作用机制将为治疗椎间盘退变性疾病提供新的方法,现对软骨终板退变的主要因素做如下综述。     

颈椎软骨终板钙化与颈椎间盘退变和椎体骨赘形成的关系

目的：研究颈椎软骨终板钙化与颈椎间盘退变和颈椎椎体骨赘形成的关系。方法：应用组织学方法观察颈前路环锯手术切下的18例脊髓型颈椎病和4例颈椎过伸性损伤致颈椎间盘突出患者的颈椎间盘及相邻的上下椎体标本,研究不同退变程度颈椎间盘软骨终板和椎间盘的形态学变化及椎体骨赘形成过程。结果：退变程度较轻或基本正常的颈椎间盘软骨终板结构良好,潮标清晰,退变程度较重的颈椎间盘软骨终板发生明显纤维化,潮标前移,钙化软骨和软骨下骨板增厚,退变颈椎间盘周边软骨终板潮标明显前移,钙化和骨化层增厚,形成突向外侧的椎体边缘的骨赘。结论：颈椎软骨终板的不断钙化和骨化导致颈椎间盘营养发生障碍可能是启动颈椎间盘退变的关键因素,退变椎体周边软骨终板的不断钙化和骨化是椎体骨赘形成的根本原因。     

实验性腰椎失稳致椎间盘退变的放射影像学观察

目的：探讨腰椎失稳对椎间盘的影响及其X线表现。方法：选用新西兰兔27只，随机分为手术组15只，对照组12只，手术组沿L3-L6棘突作后正中切口，剥离骶棘肌，切除棘上，棘间韧带，咬除关节突关节外后1/2，对照组作相同皮肤切口即缝合，分别于术后4，8个月对腰椎行X线检查，结果：除外手术组切口感染1只，术后2和5个月各死亡1只，其余兔存活完好至取材，术后4个月，手术组均发生腰椎后凸畸形，出现软骨终板钙化的椎间盘超过半数，8个月时，所有椎间盘软骨终板均钙化，多数椎间隙狭窄。对椎间隙楔形样变。椎间隙狭窄。终板钙化和骨赘形成4种退变征象发生频数的统计分析显示，手术组与对照组间的差异具有显著性意义。结论：脊柱稳定对保持椎间盘生理功能意义重大，脊柱失稳可诱发椎间盘退变，后凸畸形和软骨终板钙化是失稳诱发的腰椎间盘退变早先发生和常见的X线征象。     

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     

影响椎间盘退变生物化学改变的因素

椎间盘退卞的生物化学改变表现为 :蛋白多糖含量减少 ,硫酸角质素与硫酸软骨素的比例增加 ,Ⅰ型型胶原增多 ,Ⅱ型胶原减少 ,水分减少等 ,这一变化严重影响了椎间盘的生物力学特性 ,由此构成了椎间盘突出的病理基础。近年来 ,随着分子生物学、分子免疫学等医学基础学科的迅速发展 ,椎间盘退变生物化学改变及其影响因素等方面的研究取得了一些进展 ,现在综述如下 :1　应力对椎间盘退变的生物化学影响椎间盘由四周的纤维环、中心的髓核及上下软骨终板组成。正常椎间盘髓核呈流体静压状态 ,椎间盘内压为轴间压载荷的 1.3～ 1.5倍 ,当外载荷达 2 …     

椎间盘退变与生物力学

椎间盘退变的因素众多,生物力学是目前学者研究的热点之一。生物力学与椎间盘退变关系密切,可在椎间盘退变基础上进一步加速退变发生进程。生物力可直接使软骨终板发生细胞凋亡并出现Modic退变,也可间接影响椎间盘营养途径。生物力影响椎间盘细胞生物代谢平衡,使细胞内蛋白多糖、胶原纤维及基质金属蛋白酶等物质的合成与分解发生变化,改变椎间盘生物学功能,从而进一步加快椎间盘退变发生进程。     

椎间盘退变与生物力学

椎间盘退变的因素众多,生物力学是目前学者研究的热点之一。生物力学与椎间盘退变关系密切,可在椎间盘退变基础上进一步加速退变发生进程。生物力可直接使软骨终板发生细胞凋亡并出现Modic退变,也可间接影响椎间盘营养途径。生物力影响椎间盘细胞生物代谢平衡,使细胞内蛋白多糖、胶原纤维及基质金属蛋白酶等物质的合成与分解发生变化,改变椎间盘生物学功能,从而进一步加快椎间盘退变发生进程。     

细胞外囊泡治疗椎间盘退变的研究进展

目的 综述细胞外囊泡（extracellular vesicles,EVs）治疗椎间盘退变（intervertebral disc degeneration,IVDD）的机制研究进展。方法 查阅国内外相关文献,总结EVs的生物学特性以及其治疗IVDD的作用机制。结果 EVs是一类由多种类型细胞分泌的双层脂质膜结构的微小囊泡,通过自身含有的生物活性物质,参与细胞间信息交流,在细胞炎症、氧化应激、衰老、凋亡、自噬等方面发挥重要作用。EVs能通过改善髓核、软骨终板、纤维环的病理生理状态,发挥延缓IVDD的作用。结论 EVs有望成为治疗IVDD的新策略,但具体机制有待进一步研究。     

椎间盘退变影响因素研究进展

椎间盘退变是由多种因素影响所致。长期过高和过低的压力负荷均为椎间盘退变的病因之一。近年研究证实软骨终板钙化引起的椎间盘营养供应减少可能是启动椎间盘退变的关键因素。椎间盘老化或营养供应障碍时椎间盘细胞合成一些细胞因子,影响细胞活性和细胞间信息交流,导致细胞凋亡。椎间盘内环境改变后激活潜伏状态的降解酶,使椎间盘基质分解加速,导致椎间盘退变。该文就生物力学、营养、细胞凋亡、细胞因子及降解酶等因素对椎间盘退变的影响及作用机制,作一综述。     

腰椎椎间盘退行性变大动物模型的建立方法

<正>椎间盘退行性变(IDD)是脊柱外科的常见病和多发病,随着人口老龄化进程的加速,其发生率大幅上升~([1-2])。IDD是引起腰背痛的主要原因~([3-4]),为了寻求治疗腰背痛的有效手段,IDD与椎间盘再生的基础研究近年来受到了广泛关注。由于穿刺或者椎间盘造影会破坏椎间盘完整性,加速退行性变,在人体上进行的椎间盘研究只能进行观察而不能开展直接干预的有创研究,而动物模型在许多方面可以模拟人体IDD的发生过程,从而可     

"穿刺抽取髓核"诱导腰椎间盘退变的时间相关性评估

目的对穿刺纤维环抽取髓核诱导的腰椎间盘退变模型，进行时间相关的放射学和组织学评估，明确椎间盘退变程度的时间相关性。方法1岁山羊12只，以粗针穿刺纤维环抽取髓核（L1，2-15，6）建立腰椎间盘退变模型。术后第2、4、8、16周分别行放射学观察、髓核蛋白多糖（GAG）定量、组织学及微观结构评估。结果影像学示术后16周椎间隙高度显著降低（P〈0．01），但各椎间盘间差异无统计学意义（P〉0．05）。GAG定量示所有节段髓核内GAG含量随时间持续下降（P〈0．01），但与椎间盘序列间无相关性。大体标本及组织学观察显示，椎间盘退变组织学表现与抽取髓核后时间显著相关：术后2周组织学未见明显异常；4周始出现退变表现；16周时髓核已近完全纤维化。电镜观察示术后2—16周，髓核细胞从基本正常至大量凋亡，髓核基质逐渐纤维化。结论针刺抽取髓核法是较理想的腰椎间盘退变模型诱导方法。本研究观察16周，椎间盘退变未见缓解及自行修复，诱发的退变严重度与术后时间因素显著相关，而与椎间盘节段序列间无相关性。该模型在术后2周尚未出现明显组织学改变，或许是进行干预的良好时机。     

腰椎间盘退变动物模型的建立及影像学改变

目的建立腰椎间盘退变的动物模型。方法取新西兰大白兔6只,采用腹膜后入路进行腰椎手术,L3/L4椎间盘作为对照椎间盘;L4/L5椎间盘作为假手术椎间盘,只进行暴露;L5/L6椎间盘作为处理椎间盘,手术暴露后用24 G针头从椎间盘的前外侧针刺3次。4周后通过X线片观察针刺损伤对椎间盘高度的影响,通过MRI观察椎间盘在针刺损伤后退变的程度。结果腹膜后入路可以很好的显露新西兰大白兔腰椎间盘,所有动物均成活至术后4周,统计学分析说明针刺、手术暴露以及对照对术后4周椎间盘高度、MRI的T2加权信号强度的影响不同。用Newman-Keuls法对3样本均数两两比较结果显示：L3/L4与L4/L5之间的均数比较P〉0.05;L3/L4和L5/L6之间的均数比较P〈0.01;L4/L5和L5/L6之间的均数比较P〈0.01。结论术后4周针刺损伤实验动物椎间盘可以造成椎间盘高度、MRI的T2加权信号强度的降低,具有统计学意义。椎间盘损伤是造成椎间盘退变的原因之一。     

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。     

The lumbar intervertebral disc: From embryonic development to degeneration

Lumbar intervertebral discs (IVDs) are prone to degeneration upon skeletal maturity. In fact, this process could explain approximately 40% of the cases of low back pain in humans. Despite the efficiency of pain-relieving treatments, the scientific community seeks to develop innovative therapeutic approaches that might limit the use of invasive surgical procedures (e.g., spine fusion and arthroplasty). As a prerequisite to the development of these strategies, we must improve our fundamental knowledge regarding IVD pathophysiology. Recently, several studies have demonstrated that there is a singular phenotype associated with Nucleus pulposus (NP) cells, which is distinct from that of articular chondrocytes. In parallel, recent studies concerning the origin and development of NP cells, as well as their role in intervertebral tissue homeostasis, have yielded new insights into the complex mechanisms involved in disc degeneration. This review summarizes our current understanding of IVD physiology and the complex cell-mediated processes that contribute to IVD degeneration. Collectively, these recent advances could inspire the scientific community to explore new biotherapeutic strategies.     

一氧化氮合酶抑制剂对延缓腰椎间盘退变的影响

目的　探讨一氧化氮合酶(NOS)抑制剂L N6 亚氨乙基 赖氨酸(L NIL)和S 甲基异硫脲(SMT)对退变腰椎间盘组织代谢的影响。方法　无菌条件下,取2 0例腰椎间盘突出症患者的椎间盘组织体外培养,分别加入1mmol/L浓度的SMT和L NIL ,培养72h后,通过检测硝酸盐和亚硝酸盐的含量来观察椎间盘NO的释放量及NOS的活性;原位杂交法检测椎间盘组织iNOSmRNA和MMP3mRNA的表达。培养10d后,化学比色法观察椎间盘蛋白多糖含量和羟脯氨酸释放量的变化。结果　L NIL组髓核和纤维环NO释放量(65 .6±4.5 ,68.8±5 .7) μmol/L和SMT组髓核和纤维环NO释放量(69.5±6.5 ,69.1±6.1) μmol/L较对照组NO释放量(10 7.9±4.4,93 .1±5 .9) μmol/L明显减少(P <0 .0 1)。L NIL组和SMT组髓核组织中蛋白多糖含量(5 1.3±9.6,48.2±8.5 )kg/L ,比对照组(3 2 .1±6.4)kg/L明显增加(P <0 .0 1) ,羟脯氨酸释放量(1.1±0 .4,1.2±0 .5 )kg/L比对照组(3 .4±0 .8)kg/L显著减少(P <0 .0 1) ;同时,原位杂交法未检测到iNOSmRNA和MMP3mRNA的表达。结论　NOS抑制剂L NIL和SMT能抑制过量NO的释放,对延缓椎间盘退变具有积极的作用     

Correlation of radiographic and MRI parameters to morphological and biochemical assessment of intervertebral disc degeneration

Degenerative disc disease (DDD) is a common finding in MRI scans and X-rays. However, their correlation to morphological and biochemical changes is not well established. In this study, radiological and MRI parameters of DDD were assessed and compared with morphological and biochemical findings of disc degeneration. Thirty-nine human lumbar discs (L1–S1), age 19–86 years, were harvested from eight cadavers. Within 48 h postmortem, MRIs in various spin-echo sequences and biplanar radiographs of intact spines were obtained. Individual discs with endplates were then sectioned in the mid-sagittal plane and graded according to the morphological appearance. Samples from the nucleus of each disc were harvested for biochemical analysis including water and proteoglycan contents. On MRIs, T2-signal intensity, Modic changes, disc extension beyond the interspace (DEBIT), nucleus pulposus shape, annular tears, osteophytes and endplate integrity were graded. On radiographs, an independent observer classified the parameters disc height, endplate sclerosis, osteophytes, Schmorls nodes, intradiscal calcifications and endplate shape. General linear-regression models were used for statistical analysis. Backward elimination with a 10% significance cut-off level was used to identify the most significant parameters, which then were summed to create composite scores for radiography, MRI and the combination of both methods. The grading was performed by three observers, and a reliability analysis using Cronbachs alpha model was used to control interobserver agreement. The three radiographic parameters height-loss, osteophytes and intradiscal calcifications correlated significantly with the morphological degree of degeneration (p<0.001, R²=642). Significant differences of even one morphological grade could also be differentiated in the composite radiological score (p<0.05), except at the extremes between grades 1 and 2 and grades 4 and 5. All MRI parameters correlated significantly with the morphological grade (p<0.05); however Modic changes, T2-intensity and osteophytes accounted for 83% of the variation in the data. T2-signal intensity correlated significantly with H₂O and proteoglycan content (p<0.001), and was best for detecting highly degenerated discs. Regression showed that the combined score was better correlated with the morphological grade (p<0.001, R² =775) than either the composite radiographic (p<0.001, R² =642) or composite MRI (p<0.001, R² =696) alone. Based on the combined score, a backwards elimination of the regression was performed, in which the parameters Modic changes, and T2-intensity loss (MRI) as well as calcifications (X-ray) accounted for 87% of the variability. The interobserver validation showed a high correlation for all three scores (Cronbachs alpha values ranging from 0.95 to 0.97). Conclusion: selective imaging parameters and a newly created scoring scheme were found to correlate with disc degeneration as determined in a morphological manner. Surprisingly, radiographic parameters were able to distinguish different stages of degeneration, whereas MRI could only detect advanced stages of disc degeneration. We conclude that X-rays may remain a cost-effective, non-invasive in vivo-grading method to detect early disc degeneration, and, combined with MRI, correlate best with morphological and biochemical assessment of disc degeneration.     

Histochemical and ultrastructural observations on brown degeneration of human intervertebral disc

Thirty-eight fresh human intervertebral discs collected during anterior interbody fusion surgery were histochemically and ultrastructurally analyzed for pigments. Macroscopically, five stages of degeneration were classified according to the color, fibrosis, and fragility of the nucleus pulposus of the discs. In order to demonstrate lipofuscin granules, specimens were subjected to special staining procedures, including carbol fuchsin lipofuscin stain, the Schmorl's reaction, and autofluorescence. Lipofuscin granules were distributed from the inner layer of the annulus fibrosus to the nucleus pulposus. Such granules were numerous in cases of slight or severe degeneration, whereas fewer granules were found in cases of moderate degeneration. However, the stage of macroscopic degeneration of the intervertebral disc did not necessarily correlate with the incidence of lipofuscin granules. By ultrastructural observation, the morphological features of the components of the intervertebral disc and the ultrastructure of the lipofuscin granule were clarified. The ultrastructure of the "brown degeneration" disc exhibited markedly increased amorphous electron-dense bodies located among collagen fibrils in the matrix.     

Intervertebral disc degeneration - an autopsy study

This is an autopsy analysis of 126 thoracolumbar spines. Extensive histomorphological examination identified microscopic changes in the nucleus and annulus fibrosus before any gross or radiological changes were evident. Histomorphological evidence of microavulsion of the attachment of the annulus fibrosus from its mooring at the margin of the cartilaginous endplate of the vertebral body suggests that forces (compression, distraction, rotation) applied during movement are contributing factors to the pathogenesis of degenerative disc disease.