椎间失稳致兔椎间盘退变磁共振影像计量分析

目的 :探讨由于椎间失稳诱发的椎间盘退变在磁共振成像 (magneticresonanceimaging ,MRI)中的表现。方法 :选用新西兰兔 15只 ,随机分为手术组 9只、对照组 6只 ,手术组沿L3～ 6棘突作后正中切口 ,剥离骶棘肌和关节突附丽肌肉 ,切除棘上、棘间韧带和关节突关节外后 1/ 2 ;对照组作相同皮肤切口即缝合。所有动物在标准条件下饲养 ,分别于术后 2、 4、 8个月行腰椎MRI检查及髓核信号值测量。结果 :术后 2～ 8个月 ,对照组腰椎未见异常 ,而手术组L3～ 6椎间盘则相继出现T2 加权像低信号、腰椎后凸畸形、T1加权像低信号、椎间盘后突和硬膜囊受压等改变。对手术组手术节段及其邻近节段椎间盘髓核信号值的定量分析显示 ,T2 加权像信号值减低在术后 2、 4、8个月均具有统计学意义 ,而T1加权像信号值减低在术后 8个月具有统计学意义 ;T2 信号值减低主要发生于术后 2个月 ,T1信号值减低发生于术后 8个月。结论 :脊柱失稳可诱发椎间盘退变。髓核T2 加权像低信号是椎间盘退变的早期和先发征象 ,T1加权像显示形态改变较好 ,但T1信号值在退变早期变化不明显。     

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。     

兔椎间失稳软骨终板退变的实验研究

[目的]通过电镜研究软骨终板在椎间失稳环境下的退变过程,为椎间盘退变的治疗提供新的思路和方法.[方法]取48只6个月龄日本大耳白兔,雌雄不限,体重为(2.5±0.2)kg,随机进行分组,分为对照组和实验组,对照组为21只;实验组为27只;先将实验组兔腰背部皮毛剪除,用安定注射液1.25 mg/kg、氯胺酮0.02 g/kg、阿托品0.125 mg/kg顺次耳缘静脉注射麻醉后,俯卧固定于手术台上,用1%碘伏消毒手术区域,以髂嵴平对椎间隙(即L6.7)为中心,从正中取一长约4 cm纵行切口,切开皮肤及皮下组织,锐性分离,暴露棘突、椎板及上下关节突,将附着于棘突、椎板及小关节的肌肉全部分离开,然后依次切除L6.7棘上及棘间韧带,咬除第6腰椎两侧下关节突,造成椎间失稳,用无菌生理盐水冲洗切口,依次缝合各层组织;术后动物在笼中自由活动.实验组分别在术后2个月、4个月、6个月取材,对照组在相同条件下饲养后2个月、4个月、6个月取材;对椎间盘软骨终板用透射电镜观察软骨终板的结构,以综合判断软骨终板的退变过程.[结果]椎间失稳可导致椎问软骨终板胶原纤维结构由整齐有序、排列紧密向杂乱无章、排列松散退变.[结论]椎间失稳能明显导致椎间软骨终板的退变.     

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。     

椎间盘退变的分子生物学研究进展

据资料表明 ,美国人在一生中发生下腰痛的概率为 6 0 %～ 80 % ,成人丧失劳动力的原因中 ,下腰痛排第 3位。椎间盘退变 (ｉｎｔｅｒｖｅｒｔｅｂｒａｌｄｉｓｋｄｅｇｅｎｅｒａｔｉｏｎ ,ＩＶＤＤ)是下腰痛的一种常见病因。目前 ,临床上对下腰痛的治疗主要为保守治疗和手术治疗。手术治疗根据手术原理不同分为椎间盘切除和 /或融合术及人工椎间盘置换术。近年来前者取得了长足的进步 ,成为目前临床治疗的主要方式 ,但由于椎间盘切除和脊柱融合后 ,椎间盘的生物学环境发生改变 ,手术相邻节段退变加速。远期效果不佳。后者虽近期效果佳 ,但远…     

椎间盘退变机理的研究进展

椎间盘是由多种结缔组织构成的高度特异性结构 ,这些成分有序合理的组织是椎间盘行使正常功能的基本要求。在椎间盘的结构组成中 ,胶原和蛋白多糖两种大分子化合物起关键作用。随着年龄增加 ,椎间盘逐渐发生退行性变化 ,在退变椎间盘中 ,胶原类型发生很大变化 ,甚至完全转换[1] ;蛋白多糖含量下降 ,其中呈聚集状态的蛋白多糖下降尤为明显 ,非聚集状态蛋白多糖比例相对增加。另外 ,硫酸软骨素浓度下降 ,硫酸角质素浓度增加[2 ] 。因此 ,伴随年龄增大所引起的椎间盘老化或退变可能是基质合成和破坏之间不平衡所引起的。到底哪种成分在椎间盘退…     

尼古丁诱发椎间盘退变的实验研究

[目的]观察皮下注射尼古丁大鼠椎间盘中IL-1β阳性细胞表达率的变化,探讨尼古丁诱发椎间盘退变的可能机制。[方法]选用10~11周龄雄性SD大鼠30只,按照随机分配的原则分为3组,对照组10只,每天皮下注射生理盐水1.5 ml/kg,共注射8周;实验组2组,每组各10只,每天皮下注射尼古丁3 mg/kg(相当于成人每天抽40支香烟~([1])),分别注射2、8周。达到注射时间后,各组分别取出L_4/L_5椎间盘组织制作切片(由于人体椎间盘退变多发生在L_4/L_5椎间盘),行HE染色及IL-1β免疫组化染色,观察椎间盘退变情况及IL-1β阳性细胞率的表达情况。[结果]HE染色结果显示,尼古丁注射2周实验组大鼠椎间盘与对照组比较无明显变化,少数出现1级退变。尼古丁注射8周实验组大鼠椎间盘纤维环结构紊乱,出现3~4级退变。免疫组化染色结果显示,对照组IL-1β阳性细胞表达率为(7.0±0.34)%,实验组IL-1β阳性细胞表达率分别为(32.1±2.69)%、(78.6±2.59)%。对数据进行统计分析,三组间差异具有统计学意义。[结论]尼古丁可能通过刺激机体合成和释放IL-1β而诱发椎间盘退变。     

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。     

一氧化氮与椎间盘退变

椎间盘突出的基本病理改变是椎间盘退变,一氧化氮参与此过程。一氧化氮在退变椎间盘中有炎症因子样作用及热痛觉过敏作用,对继发于颈,腰椎间盘突出的神经根疼痛发挥作用,对椎间盘基质的影响主要是介导抑制软骨细胞合成蛋白多糖作用。     

椎间盘退变基因治疗的研究动态

椎间盘退变疾病(disc degeneration diease,DDD)是一种发病率及致残率很高的疾病,目前常规的治疗方法包括：药物治疗、类固醇注射封闭、理疗以及手术治疗等。近来微创手术方面取得长足进步,出现了如椎间盘镜(endoscopic discectomy)和经皮椎间盘切除术(percutaneous discectomy)等方法。但是,这些治疗措施仅着眼于改善疾病的临床症状,而不是从根本上减缓或中止退变进程。基因治疗作为近年来兴起的一种治疗方法,可在分子水平进行调控,从而为延缓或逆转疾病进程提供了可能。本文就目前椎间盘退变基因治疗的研究现状及进展进行综述。     

双侧关节突关节切除诱发椎间盘退变的磁共振计量分析

[目的]探讨新西兰大白兔腰椎关节突关节破坏诱发出椎间盘退变的核磁共振改变。[方法]30只新西兰大白兔,体重2.25~2.95kg,雄性。随机分为骨性手术组和软组织手术组。软组织手术组仅骨膜下剥离L3~7的椎旁肌肉;骨性手术组完整切除L4、5双侧下关节突和L5棘突,保留L5、L6上关节突。骨性手术组L4、5、L5、6椎间盘为实验组椎间盘,上下相邻的L3、4、L6、7为自身对照组椎间盘。软组织手术组L4、5、L5、6椎间盘为实验对照组椎间盘。术后1、2、4及8个月行核磁共振检查。将实验所得的L3、4、L4、5、L5、6、L6、7T2WI轴位像输入电脑,用KONTRONIBAS2.0全自动图像分析系统分析图像中高信号区域面积占整个椎间盘面积的百分比(面积分数)并进行统计分析。[结果]新西兰大白兔T2WI矢状位像上,髓核呈均一高信号。T2WI轴位像上,髓核高信号区域位于椎间盘中央,占椎间盘横截面积50%左右。养殖1个月与8个月面积分数比较无统计学差异。随着术后时间延长,实验组椎间盘轴位像上面积分数变化显著,自身对照组次之,实验对照组最小,相同时间3组之间比较有统计学差异,相同组别术后不同时间比较有统计学差异。[结论]脊柱失稳可以诱发椎间盘退变。髓核T2WI轴位像上面积分数减小能够较早反映出椎间盘退变。     

腰椎间盘退变动物模型的建立

目的 制备椎问盘退变动物模型.方法 将48只新西兰大白兔随机分为骨性手术组和软组织手术组.骨性手术组L4L5、L5L6为实验组椎间盘,L3L4、L6L7为自身对照组;软组织手术组L4L5、L5L6为实验对照组椎问盘.术后1、2,4及8个月行MRI及分子生物学检查.结果 (1)MRI:兔髓核位于椎间盘中央,占椎间盘横截面积50%左右.术后1、2、4及8个月,3组椎间盘横断面T2高信号区域面积分数均逐渐减小(F=96.2～1544.4,P<0.01);术后相同时间段,实验组面积分数最小,自身对照组次之,实验对照组最高,差异有统计学意义(F=125.7～1850.6,P<0.01).(2)分子生物学:蛋白多糖、胶原为椎间盘主要细胞外基质,术后1、2、4及8个月,3组椎间盘蛋白多糖、Ⅱ型胶原表达量进行性下降(F=148.2～1544.4,P<0.01),Ⅰ型胶原表达量进行性上升(F=94.3～579.6,P<0.01).术后相同时间段,实验组蛋白多糖、Ⅱ型胶原最小,自身对照组次之,实验对照组最高(F=135.5～3520.6,P<0.01);Ⅰ型胶原表达量实验组高于实验对照组、自身对照组(F=7.8～143.1,P<0.01).结论 破坏关节突关节成功制备出椎间盘退变动物模型.     

双侧关节突关节切除致椎间盘退变的影像学观察

[目的]探讨新西兰大白兔腰椎关节突关节破坏能否诱发出椎间盘退变的影像学改变。[方法]45只新西兰大白兔，体重2．25～2．95kg，雄性。随机分为骨性手术组和软组织手术组。软组织手术组骨膜下剥离L3至b的椎旁肌肉：骨性手术组完整切除L4、5，双侧下关节突、L5棘突，保留L5、6上关节突。骨性手术组L4、5、L5、6椎间盘为实验组椎间盘，上下相邻的L3、4、L6、7，为自身对照组椎间盘。软组织手术组L4、5、L5、6。椎间盘为实验对照组椎间盘。术后1、2、4及8个月行X线检查。计数不同组别椎间盘退变的异常X线征象发生频数并进行统计分析。[结果]术后1个月，实验组椎间盘开始出现软骨终板钙化。随着时间推移，椎间隙狭窄、椎体边缘骨赘、软骨终板钙化发生频数逐渐增多，与实验对照组、自身对照组比较具有统计学差异。术后8个月，骨性手术组中大部分动物出现以L4、5、或L5、6为中心的角状后凸畸形。[结论]L4、5、L5、6。关节突关节破坏导致椎间失稳，椎间失稳后可以诱发出椎间盘退变的影像学改变。     

Gene therapy for intervertebral disk degeneration

Intervertebral disk degeneration is a common and potentially debilitating disease process affecting millions of Americans and other populations each year. Current treatments address resultant symptoms and not the underlying pathophysiology of disease. This has spawned the development of biologic treatments, such as gene therapy, which attempt to correct the imbalance between catabolism and anabolism within degenerating disk cells. The identification of therapeutic genes and development of successful delivery systems have resulted in significant advances in this novel treatment. Continued investigation of the pathophysiology of disk degeneration, however, and safety mechanisms for the application of gene therapy are required for clinical translation.     

Urodynamic study in the neurogenic bladder dysfunction caused by intervertebral disk hernia

AIMS: To discuss the clinical significance of urodynamic studies in neurogenic bladder dysfunction caused by intervertebral disk hernia. METHODS: Thirty patients with neurogenic bladder dysfunction caused by intervertebral disk hernia were divided into three groups according to the category of detrusor muscle activity: neurogenic detrusor overactivity without detrusor sphincter dyssynergia (DSD), neurogenic detrusor overactivity with DSD, or detrusor underactivity. The patients were divided into three groups according to the condition of urinary retention and incontinence: urinary retention, urinary incontinence, or neither urinary retention nor urinary incontinence. Also they were divided into three groups according to the location of the intervertebral disk hernia: cervical hernia, thoracic hernia, or lumbar hernia. All patients underwent computer tomography (CT), magnetic resonance imaging (MRI), and urodynamic study. The results were analyzed statistically. RESULTS: There was significant correlation between the category of detrusor muscle activity, bladder compliance (BC, P < 0.05), and the pressure at maximum flow (P(det,Qmax), P < 0.01). There were significant differences in post void residual (PVR), cystometric capacity (CC), and maximum flow rate (Qmax) between the three groups of urinary retention, urinary incontinence, and the group of neither retention nor incontinence (P < 0.05). There was statistical correlation between the location of the intervertebral disk hernia and the urodynamic results. There was significant correlation between the BC (the threshold was 15 ml/cmH(2)O), detrusor pressure (Pdet, the threshold was 40 cmH(2)O), DSD, the location of intervertebral disk hernia, and the upper urinary tract lesion (P < 0.01). CONCLUSIONS: Urodynamic studies are indispensable in the classification, diagnosis, treatment, and prognosis of the neurogenic bladder dysfunction caused by intervertebral disk hernia.     

Histological and reference system for the analysis of mouse intervertebral disc

A new scoring system based on histo‐morphology of mouse intervertebral disc (IVD) was established to assess changes in different mouse models of IVD degeneration and repair. IVDs from mouse strains of different ages, transgenic mice, or models of artificially induced IVD degeneration were assessed. Morphological features consistently observed in normal, and early/later stages of degeneration were categorized into a scoring system focused on nucleus pulposus (NP) and annulus fibrosus (AF) changes. “Normal NP” exhibited a highly cellularized cell mass that decreased with natural ageing and in disc degeneration. “Normal AF” consisted of distinct concentric lamellar structures, which was disrupted in severe degeneration. NP/AF clefts indicated more severe changes. Consistent scores were obtained between experienced and new users. Altogether, our scoring system effectively differentiated IVD changes in various strains of wild‐type and genetically modified mice and in induced models of IVD degeneration, and is applicable from the post‐natal stage to the aged mouse. This scoring tool and reference resource addresses a pressing need in the field for studying IVD changes and cross‐study comparisons in mice, and facilitates a means to normalize mouse IVD assessment between different laboratories. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:233–243, 2018.     

Canonical Wnt signaling in the notochordal cell is upregulated in early intervertebral disk degeneration

The notochordal cell (NC) of the nucleus pulposus (NP) is considered a potential NP progenitor cell, and early intervertebral disk (IVD) degeneration involves replacement of NCs by chondrocyte-like cells (CLCs). Wnt/β-catenin signaling plays a crucial role in maintaining the notochordal fate during embryogenesis, but is also involved in tissue degeneration and regeneration. The canine species, which can be subdivided into non-chondrodystrophic and chondrodystrophic breeds, is characterized by differential maintenance of the NC: in non-chondrodystrophic dogs, the NC remains the predominant cell type during the majority of life, with IVD degeneration only occurring at old age; conversely, in chondrodystrophic dogs the NC is lost early in life, with concurrent degeneration of all IVDs. This study investigated Wnt/β-catenin signaling in the healthy, NC-rich NP and early degenerated, CLC-rich NP of both breed types by immunohistochemistry of β-catenin and relative gene expression of brachyury and cytokeratin 8 (notochordal markers) and Wnt targets axin2, cyclin D1, and c-myc. Both NCs and CLCs showed nuclear and cytoplasmic β-catenin protein expression and axin2 gene expression, but β-catenin signal intensity and Wnt target gene expression were higher in the CLC-rich NP. Primary NCs in monolayer culture (normoxic conditions) showed Wnt/β-catenin signaling comparable to the in vivo situation, with increased cyclin D1 and c-myc gene expression. In conclusion, Wnt/β-catenin signaling activity in the NC within the NC-rich NP and in culture supports the role of this cell as a potential progenitor cell; increased Wnt/β-catenin signaling activity in early IVD degeneration may be a reflection of its dual role.     

Biomechanics of intervertebral disk degeneration

Degenerative changes in the material properties of nucleus pulposus and anulus fibrosus promote changes in viscoelastic properties of the whole disc. Volume, pressure and hydration loss in the nucleus pulposus, disk height decreases and fissures in the anulus fibrosus, are some of the signs of the degenerative cascade that advances with age and affect, among others, spinal function and its stability. Much remains to be learned about how these changes affect the function of the motion segment and relate to symptoms such as low back pain and altered spinal biomechanics.     

Correlation between bone mineral density and intervertebral disk degeneration in pre- and postmenopausal women

 The purpose of this study was to investigate the relationship between intervertebral disk degeneration and bone mass. Magnetic resonance imaging was performed to evaluate lumbar disk degeneration according to Thompson's classification (grades 1 and 2, normal disk; grades 3, 4, and 5, degenerated disk), and bone mineral density (BMD) in the lumbar vertebrae, radius, and calcaneus was measured by dual-energy X-ray absorptiometry for 90 women (22–74 years old). The relationship between the grade of intervertebral disk degeneration and the BMD (Z score) was analyzed in pre- and postmenopausal women. In premenopausal women, BMD was significantly higher at all measured sites in the degenerated disk group judged at the L5–S1 level than in the normal disk group (P < 0.05). In postmenopausal women, BMD was significantly higher at the anteroposterior L2–L4, lateral L3, and calcaneus in the degenerated disk group judged at the L2–L3 level than in the normal disk group (P < 0.05). BMD at the anteroposterior L2–L4 and calcaneus was significantly higher in the degenerated disk group judged at the L3–L4 level than in the normal disk group (P < 0.05). In conclusion, the BMD of not only the lumbar vertebrae but also the calcaneus and radius was mutually related to lumbar intervertebral disk degeneration from an early stage of degeneration. Received: May 16, 2002 / Accepted: July 31, 2002 Offprint requests to: Y. Nanjo