退变腰椎间盘组织中碱性成纤维细胞生长因子的表达研究

目的 探讨碱性成纤维细胞生长因子（basic fibroblast growth factor,bFGF)在正常和退变椎间盘组织中的表达情况。方法 交30例来源于腰椎间盘突出症患者手术中所取得的椎间盘组织（观察组，男11例，女19例；年龄25－78岁，平均48岁；病程3个月－30年，平均9年11个月）与6例来源于脊柱侧凸患者前路松解术所取得的椎间盘组织（对照组，男女各3例，年龄10－17岁，平均14.2岁）进行对比，首先经病理组织学检查证实为退变椎间盘组织和政党椎间盘组织，然后将两组椎间盘组织分别通过免疫组织化学方法和原位杂交方法，检测各自椎间盘组织中的bFGF及其mRNA的表达。观察组30例均为退变椎间盘组织，免疫组化阳性率为90％（27／30），原位杂交阳性率为20％（6／30）；对照组6例均为正常椎间盘组织，其免疫组及原位杂交均为阴性，两组间免疫组化方法检测阳性率在统计学上差异有非常显著性意义。结论 bFGF在正常和退变椎间盘组织中表达的差异有显著性意义。提示 bFGF可能作为增生刺激因子促进椎间盘组织中的软骨细胞增生和细胞外基质合成，进而加速椎间盘退变。     

Neovascularization of nucleus pulposus. A diagnostic feature of intervertebral disc prolapse

STUDY DESIGN: Seventy-five surgically excised prolapsed intervertebral discs were histopathologically evaluated. Fifteen prospective normal cadaveric discs were used as control specimens. OBJECTIVE: To compare the morphologic features between the prolapsed and normal discs. SUMMARY OF BACKGROUND DATA: The histologic criteria were edge neovascularization of the fibrocartilage, chondrocyte cloning, fibrillation with fraying, and granular change. METHODS: Sections stained with hematoxylin and eosin, Van Gieson's, and toluidine blue were studied. The presence or absence of edge neovascularization was noted. The other criteria were graded based on a semiquantitative scoring system. RESULTS: Edge neovascularization was observed in 56% of the discs in the test group and in none of the control specimens. Fibrillation with fraying was the most significant finding in the test group (P < 0.001). Although the mean grades were higher in the test group, they did not predict the presence of edge neovascularization. CONCLUSIONS: Edge neovascularization was the most significant finding to confirm disc prolapse. Fibrillation with fraying, was observed more frequently in prolapsed intervertebral discs and the grades of fibrillation with fraying, chondrocyte cloning, and granular change were significantly higher in the test group. Pathologists can usually agree on the presence or absence of a particular histologic characteristic but are rarely consistent when they estimate the degree. Simple, reproducible agreed-on criteria are needed before semiquantitative evaluations become reliable.     

Radiographic appearances in lumbar disc prolapse

The pre-operative lumbar spine radiographs of 200 consecutive patients who had undergone discectomy for prolapsed intervertebral disc were reviewed. Prolapse was recognized as bulging or sequestration of the disc with consequent root compromise. Measurement of the lumbar level of the interiliac line was shown to correlate with the level of disc prolapse and the incidence of transitional vertebrae at the lumbosacral junction was significantly higher than normal. A pathological value for the lumbosacral angle could not be identified.     

An in vivo model of degenerative disc disease.

Although the precise etiology of low back pain is disputed, degeneration of the intervertebral disc is believed to play an important role. Many animal models have been described which reproduce the changes found in degenerative disc disease, but none allow for efficient, large-scale testing of purported therapeutic agents. The purpose of this study was to develop a simple animal model resembling degenerative disc disease using the intervertebral discs found in the tails of rats. The proximal two intervertebral discs in the tails of 20 rats were injected with either chondroitinase ABC or control (phosphate buffered saline, PBS). The tails were harvested at 2 weeks, and measurements were made of intervertebral disc height (measured radiographically and histologically), biomechanics (stiffness, hysteresis, and residual deformation), and histologic appearance. Treatment with chondroitinase ABC resulted in a significant loss in intervertebral disc height (radiographic intervertebral disc height, p=0.001; histologic intervertebral disc height, p<0.001) and significant increases in all biomechanical parameters (stiffness, p<0.001; hysteresis, p=0.006; residual deformation, p=0.004) compared to PBS controls. Intervertebral discs treated with chondroitinase ABC had significantly lower histologic grades for each grading category (nucleus pulposus (NP), annulus fibrosus, and proteoglycan staining) compared to controls. The results of injury with chondroitinase ABC were similar to the findings in degenerative disc disease: reduced intervertebral disc height, diminished proteoglycan content, loss of NP cells, and increased stiffness of the disc. Thus, the model appears to be a reasonable tool for the preliminary in vivo evaluation of proposed treatments for degenerative disc disease.     

阻断双侧终板营养途径构建山羊椎间盘退变模型

目的通过建立山羊腰椎双侧终板营养途径阻断的动物模型,观察椎间盘退变(IDD)的情况,研究椎间盘营养途径与IDD的相关性。方法选取8只24月龄雌性关中山羊,每只山羊L2~3、L3~4作为实验椎间盘,麻醉后在平行于终板2 mm的椎体骨质处造成骨缺损,并使用骨水泥填塞,阻断椎体和终板之间的营养通路,L1~2、L4~5作为对照椎间盘。分别于术后4、12、24、48周行X线、MRI检查,各时间点随机处死2只山羊,采集椎间盘标本,计算骨水泥有效阻断面积、椎间高度指数(DHI)和Pfirrmann分级,并行HE、Masson三色、蛋白多糖、番红O染色组织学检查。结果术后骨水泥有效阻断面积达49.6%~69.6%(60.7%±5.3%)。术后48周时实验椎间盘DHI百分比为60.5%~81.7%(72.7%±5.6%),椎间高度丢失较对照差异有统计学意义(P<0.01);术后48周时实验椎间盘Pfirrmann分级为3~5(4.0±0.7)分,较对照差异有统计学意义(P<0.01)。组织学检查证实,实验椎间盘术后12周即发生退变,并随时间(24、48周)逐步加重。结论骨水泥填塞阻断双侧终板营养途径可以构建山羊IDD的动物模型,阻断终板营养途径可以导致IDD发生。     

Human intervertebral disc cell culture for disc disorders

Repair of degenerated intervertebral discs by engineered tissue is a clinical challenge in spinal surgery. Prerequisites are cultivation of intervertebral disc cells and determination of their biologic properties. The influence of disc damage in different spinal disorders on the outcome of disc cell cultures has not been discussed previously. This study showed the feasibility of cultivation of cells from damaged human intervertebral discs and the dependence of cellular culture properties on the underlying disc disorder. Human intervertebral disc cells were isolated from disc tissue obtained during surgical procedures for scoliosis, osteochondrosis, and disc herniation. After proliferation in monolayer culture, cells were embedded in a mixed matrix composed of fibrin and hyaluronic acid. Deoxyribonucleic acid content, hydroxyproline content, and proteoglycan synthesis were determined on Days 7, 14, and 21. In a three-dimensional environment only cells obtained from scoliotic and osteochondrotic discs showed significant deoxyribonucleic acid and proteoglycan synthesis. However, hydroxyproline content increased only in cells from scoliotic discs. The results of this study show that the formation of extracellular matrix components under three-dimensional culture conditions is dependent on the nature of intervertebral disc damage of the tissue processed.     

Abnormal connective tissue degrading enzyme patterns in prolapsed intervertebral discs

The collagenolytic enzyme systems in the human, normal, and prolapsed intervertebral discs have been studied. Normal discs obtained postmortem contained a novel collagenase with specificity toward Type II collagen and gelatin but with little or no activity against Type I collagen. A method whereby enzymes are detected quantitatively in extracts of human tissue using specific substrates, without prior chromatographic separation of the enzymes, has been developed and used to study 14 normal discs and 35 surgically excised prolapsed discs. No differences were observed between annulus and nucleus extracts of normal discs either in the pattern of enzymes or the quantity. The intermediate zone between nucleus and annulus was excised and was not tested. Highly significant differences were observed between the enzyme patterns of the normal and prolapsed discs. The major collagenolytic activity of normal discs is against Type II collagen and 1 alpha 2 alpha 3 alpha collagen, there is little activity toward Type I collagen and virtually none toward elastin. Conversely, the prolapsed disc is more highly active against the substrates elastin and Type I collagen than against Type II collagen or 1 alpha 2 alpha 3 alpha collagen. The individual patterns of enzymes of the 35 prolapsed discs were virtually identical. Similarly there was little internal variation between the patterns of enzymes extracted from discs, obtained postmortem, which were apparently normal. The striking difference between the normal and prolapsed disc could be an important factor in the pathogenesis of disc prolapse.     

uPA、MMP-3在退变椎间盘中的表达及意义

目的探讨尿激酶型纤溶酶原激活剂（uPA）、基质金属蛋白-3（MMP-3）在人类退变椎间盘组织中的表达变化。方法对照组为取自脊柱侧凸患者的正常腰椎间盘组织；实验组为腰椎间盘突出患者的退变椎间盘组织。分别进行免疫组织化学染色，比较2组椎间盘组织中uPA及MMP-3的光密度值。结果uPA和MMP-3在突出椎间盘组织中平均光密度值较正常椎间盘组织中的平均光密度值表达明显升高；相关分析显示突出椎间盘中uPA、MMP-3呈正相关关系。结论uPA和MMP-3均可能参与了人椎间盘组织的退变过程，且MMP-3与uPA在人类退变椎间盘组织中有相同的增高趋势。     

腰椎棘突间稳定器(Wallis)早期疗效分析

目的评价棘突间动力稳定器(Wallis)治疗腰椎退行性疾病的即时(出院前)和短期效果,探讨其适应证选择和手术技巧。方法2008年7月～2009年7月,36例腰椎退行性疾病患者共植入Wallis38套(L2/31套,L3/44套,L4/533套)。其中腰椎间盘脱出症(中央型)8例,腰椎盘脱出伴突出2例,腰椎间盘突出症伴黄韧带增厚10例,腰椎间盘突出症伴侧隐窝狭窄8例,单节退变性椎管狭窄症4例,Topping off4例。采用北美脊柱学会(North American Spine Society,NASS)问卷评价出院前患者及随访患者对手术的满意度,同时测量手术前后椎间盘终板间高度。结果手术时间30～90min,平均60min;术中出血量10～100ml,平均50ml。出院前NASS问卷显示,32例患者(88.9%)认为腰部坚实有力,术前酸乏症状消失或明显减轻。术前终板间高度降低的37个椎间盘中有31个(84%)获得1～3mm的改善。36例患者均获随访,随访时间1～12个月,平均7个月。随访期间NASS问卷总满意度为92.5%,未出现Wallis引起的并发症。结论Wallis的即时和近期疗效满意,是治疗腰椎退变性疾病的有效方法。     

Histological changes in aging lumbar intervertebral discs. Their role in protrusions and prolapses

To study the relationships between the changes due to aging in lumbar intervertebral discs and the development of protrusion or prolapse, we carried out histological studies on operative specimens of thirty-one discs, of which twenty-two had been protruded and nine, prolapsed. The specimens were obtained during twenty-nine operations for herniation of a lumbar intervertebral disc in patients who were sixty years old or older. Changes in the anulus fibrosus were more extensive in the nine prolapsed discs than in the twenty-two protruded discs. Of the nine prolapsed discs, myxomatous degeneration, fibrosis, and swollen anular fibers were found in all nine, and cysts were seen in five. Of the twenty-two protruded discs, only five showed myxomatous degeneration; ten, fibrosis; one, a cyst; and sixteen, swollen fibers. For comparison, we also studied specimens that had been obtained at operation from twenty-one other patients, twenty to fifty-nine years old, who had a prolapsed disc. The anulus showed myxomatous degeneration in all twenty-one specimens, cysts in eight, and fibrosis in ten. In addition, we examined 368 autopsy specimens from people who had been between twenty-five and eighty-five years old at the time of death. In many of the subjects who had died in the sixth decade of life or later, we found that the orientation of the inner fiber bundles of the anulus fibrosus was reversed, so that they bulged inward. The reversal appeared to be the result of myxomatous degeneration of the middle fibers of the anulus, atrophy of the nucleus, and narrowing of the disc space. These histological findings suggest explanations for the predominance of protrusions of the nucleus pulposus in patients who are less than sixty years old and of prolapse of the anulus fibrosus in the few patients who are more than sixty years old who have herniation of an intervertebral disc.     

Intervertebral mobility in the progressive degenerative process. A radiostereometric analysis

Three separate stages have previously been defined in the progressive degenerative process. The first stage, characterized as temporary dysfunction with early degenerative findings, transforms into a second period of segmental instability evidenced by a resulting deformity. With the deformity the process has reached a late stage of definitive stabilization induced by osteoligamentary repair mechanisms. To test the validity of this three-stage hypothesis, we assessed the intervertebral mobility for the two most-distal lumbar disc levels in 18 adult patients with low back pain, disc degenerative findings and no prior spinal surgery. Each spinal segment was categorized according to grade of disc degeneration: (IA) normal disc height without dehydration; (IB) normal disc height with dehydration; (II) disc height decreased by less than 50%; (III) disc height decreased by at least 50%; and (IV) disc height obliterated. The intervertebral mobility was measured by radiostereometric analysis (RSA) and compared between the categories. With the patient changing position from supine to sitting, the mean vertical translation across the 11 discs categorized as IA was 2.0 mm. A small increase in mean vertical mobility with progressive loss of disc height through the degenerative stages IB (2.2 mm, seven discs) and II (2.6 mm, ten discs) was not significant. Further degeneration to grade III meant a significant mean reduction in vertical mobility to 0.8 mm for the eight discs in that category. No discs were classified as obliterated, category IV. The corresponding values for sagittal translations were 3.0 mm, 3.1 mm, 3.6 mm and 1.7 mm for the four disc categories found. These alterations were not statistically significant. We conclude that intervertebral mobility changes throughout the degenerative process, and a stage of stabilization begins when disc height is reduced by 50%. The segmental mobility status cannot be deduced from the radiographic, degenerative disc stage, since the inter-individual differences in mobility are pronounced for the same disc status. A fully stable situation cannot be taken for granted, even when the disc is reduced by more than 50%, considering the fact that some persisting mobility was seen for most patients in category III. A preceding stage of instability, in the clinical situation proven by a resulting deformity, was not verified in this study.     

Effect of anular repair on the healing strength of the intervertebral disc: a sheep model

STUDY DESIGN: The intervertebral disc, in a sheep model, was used to assess the effect of directly repairing three different anular incisions on the subsequent healing strength of the intervertebral disc. OBJECTIVES: To assess whether directly repairing an anular defect, made at the time of lumbar discectomy, could influence the healing rate and strength of the anulus fibrosus. METHODS: Twenty-four sheep underwent a retroperitoneal approach to five lumbar disc levels. An anular incision, followed by partial discectomy was done at each exposed level. Anular incisions used in this study consisted of 1) a straight transverse slit, 2) a cruciate incision, and 3) a window or box excision. Healing strength was measured at three time intervals: 2 weeks, 4 weeks, and 6 weeks. Each anular incision type was performed on 30 lumbar discs, 10 discs in each time interval. Five discs in each time interval underwent direct repair, and five discs were left unrepaired to heal as controls. The sheep were killed at 2, 4, and 6 weeks after surgery. The lumbar spines were removed en bloc, and the intervertebral discs were subjected to pressure-volume testing to assess the anular strength of repaired versus unrepaired disc injuries at each time interval. RESULTS: Statistical analysis was performed to evaluate the effects of healing time, incision technique, and repair on the pressure-volume characteristics of the involved discs. Pressure-volume testing showed trends of stronger healing for repaired discs, but at no time interval was any significant difference found between repaired and nonrepaired anular strength. Of the nonrepaired discs, the box incision was only 40 to 50% as strong as the slit or cruciate incised discs during early healing. CONCLUSION: Direct repair of anular incisions in the lumbar spine does not significantly alter the healing strength of the intervertebral disc after lumbar discectomy.     

腰椎间盘人工髓核假体置换术临床应用初步报告

目的评价人工髓核假体(prostheticdiscnucleus,PDN)置换术治疗腰椎间盘突出症的近期效果。方法2002年3～6月,共施行PDN置换术20例,男13例,女7例,平均年龄38.4岁;均为单节段腰椎间盘突出症,其中L4-5 17例,L5S1 3例;病程6个月～10年,平均26.7个月。均采用单枚PDN置入,PR725型15例,PR925型1例,PR525型1例,PW725型2例,PW525型1例。结果所有患者术后临床症状均消失,运动功能明显改善。17例获得1～3个月随访,椎间隙高度较术前平均增加15.8%,差异有非常显著性意义(t=5.84,P<0.01), 无早期假体移位发生。术后早期并发症主要包括一过性腰部酸痛和低热。结论PDN置换术能有效恢复退行性椎间盘病变患者的椎间盘高度,近期效果肯定,多数国人适合置入单枚PR725型PDN。     

山羊腰椎间盘损伤后P物质免疫染色阳性神经纤维的分布

目的 研究山羊椎间盘损伤后的组织学改变及P物质(substance P,SP)免疫染色阳性神经纤维在损伤纤维中的分布.方法 15只山羊,用直径1.2 mm的穿刺针刀刺伤L5/L6椎间盘前纤维环全层和L6/L7后部纤维环内侧,以L4/L5椎间盘作为完整对照椎间盘.分别于损伤后3周、3个月、6个月随机处死5只山羊.观察实验...     

Patterns of lumbar disc degeneration are different in degenerative disc disease and disc prolapse magnetic resonance imaging analysis of 224 patients

Background contextExisting research on lumbar disc degeneration has remained inconclusive regarding its etiology, pathogenesis, symptomatology, prevention, and management. Degenerative disc disease (DDD) and disc prolapse (DP) are common diseases affecting the lumbar discs. Although they manifest clinically differently, existing studies on disc degeneration have included patients with both these features, leading to wide variations in observations. The possible relationship or disaffect between DDD and DP is not fully evaluated.PurposeTo analyze the patterns of lumbar disc degeneration in patients with chronic back pain and DDD and those with acute DP.Study designProspective, magnetic resonance imaging–based radiological study.MethodsTwo groups of patients (aged 20–50 years) were prospectively studied. Group 1 included patients requiring a single level microdiscectomy for acute DP. Group 2 included patients with chronic low back pain and DDD. Discs were assessed by magnetic resonance imaging through Pfirmann grading, Schmorl nodes, Modic changes, and the total end-plate damage score for all the five lumbar discs.ResultsGroup 1 (DP) had 91 patients and group 2 (DDD) had 133 patients. DP and DDD patients differed significantly in the number, extent, and severity of degeneration. DDD patients had a significantly higher number of degenerated discs than DP patients (p<.000). The incidence of multilevel and pan-lumbar degeneration was also significantly higher in DDD group. The pattern of degeneration also differed in both the groups. DDD patients had predominant upper lumbar involvement, whereas DP patients had mainly lower lumbar degeneration. Modic changes were more common in DP patients, especially at the prolapsed level. Modic changes were present in 37% of prolapsed levels compared with 9.9% of normal discs (p<.00). The total end-plate damage score had a positive correlation with disc degeneration in both the groups. Further the mean total end-plate damage score at prolapsed level was also significantly higher.ConclusionThe results suggest that patients with disc prolapse, and those with back pain with DDD are clinically and radiologically different groups of patients with varying patterns, severity, and extent of disc degeneration. This is the first study in literature to compare and identify significant differences in these two commonly encountered patient groups. In patients with single-level DP, the majority of the other discs are nondegenerate, the lower lumbar spine is predominantly involved and the end-plate damage is higher. Patients with back pain and DDD have larger number of degenerate discs, early multilevel degeneration, and predominant upper lumbar degeneration. The knowledge that these two groups of patients are different clinically and radiologically is critical for our improved understanding of the disease and for future studies on disc degeneration and disc prolapse.     

uPA、MMP-3在退变椎间盘中的表达及意义

目的探讨尿激酶型纤溶酶原激活剂（uPA）、基质金属蛋白-3（MMP-3）在人类退变椎间盘组织中的表达变化。方法对照组为取自脊柱侧凸患者的正常腰椎间盘组织；实验组为腰椎间盘突出患者的退变椎间盘组织。分别进行免疫组织化学染色，比较2组椎间盘组织中uPA及MMP-3的光密度值。结果uPA和MMP-3在突出椎间盘组织中平均光密度值较正常椎间盘组织中的平均光密度值表达明显升高；相关分析显示突出椎间盘中uPA、MMP-3呈正相关关系。结论uPA和MMP-3均可能参与了人椎间盘组织的退变过程，且MMP-3与uPA在人类退变椎间盘组织中有相同的增高趋势。     

A comparison of CT/discography, pain response and radiographic disc height

CT/discograms of 107 low-back patients were classified by annular degeneration, annular disruption, and pain response. These parameters were compared with the heights of the corresponding discs. Disc height correlated significantly with degenerative annular changes. Comparison of the painless and exact reproduction groups at the L5-S1 level showed a significant increase in exact pain reproduction in narrow discs compared with normal discs. Discs demonstrating slight degenerative changes were often painful but narrowing was detected only when degeneration increased to moderate or severe levels. Some severely degenerated discs were painless and only part of the severe group was narrow. Measuring disc height is a poor method for detecting early, painful degeneration changes.     

Effects of unisegmental disc compression on adjacent segments: an in vivo animal model

It is controversial whether fusion of discs in the spine leads to increased degeneration on the remaining discs or whether the degenerative changes are merely a part of the inevitable natural history process. To determine the effects of unisegmental compression and subsequent recovery on adjacent segments, we studied histology, radiology and intradiscal pressure using an in vivo rabbit model. Fifteen New Zealand rabbits were divided in to three groups of five. In the first group, the intervertebral disc L4–L5 of the lumbar spine was axially loaded for 28 days with an external loading device. In the second group, the intervertebral disc was compressed for 28 days and allowed to recover for an equal amount of time, with the loading device removed. Five animals underwent a sham operation, in which the external loading device was situated, but their discs remained unloaded for 28 days. The intradiscal pressure was determined in the loaded discs as well as in the cranial and caudal adjacent discs. Lateral radiographs were taken from each subjected intervertebral disc with adjacent vertebral bodies and the cranial and caudal adjacent segments. The compressed discs showed lower intradiscal pressure in comparison with the control group, which remained unloaded. In the cranial and caudal discs adjacent to the loaded discs the average intradiscal pressure was similar to the unloaded controls. The loaded discs demonstrated a significant decrease in disc space. No discs adjacent to the loaded discs changed in height. The lamellar architecture of the inner, middle, and outer annulus became more disorganized in the loaded discs. The nucleus pulposus showed increase of mucoid degeneration and increased cell death. Intervertebral discs from the control group and the adjacent discs to the compressed discs maintained their normal morphology. This study shows that mechanical loading of discs in the spine can cause rapid degeneration. Adjacent discs, however, did not change in terms of radiology, intradiscal pressure, or histology.     

MRI and discography of annular tears and intervertebral disc degeneration. A prospective clinical comparison.

We attempted to correlate the findings of MRI and discography in patients with low back pain, examining 108 lumbar intervertebral discs in 33 consecutive patients. MRI results were assessed from the intensity and shape of the signal obtained from the central part of the disc. Discography was classified according to the pattern of contrast material, the pressure accepted and the pain reproduced. All discs which were abnormal on MRI had altered patterns on discography, but 18 of the 60 discs with normal MRI had abnormal discograms. Of 39 asymptomatic discs, 33 had normal MRI signals and 24 had normal discograms. None of the 15 discs showing severe degeneration on MRI sustained high levels of intradiscal pressure, but only six of the 60 discs giving normal MRI had low pressure. With current techniques, discography is more accurate than MRI for the detection of annular pathology: a normal MRI does not exclude significant changes in the peripheral structure of the intervertebral disc which can produce low back pain.