基质金属蛋白酶-3在突出椎间盘中的表达及其意义

目的：检测椎间盘突出症的椎间盘中是否有基质金属蛋白酶－３（ＭＭＰ３）的表达,以便进一步了解椎间盘突出症的发病机制。方法：运用免疫组织化学抗生物素蛋白－生物素－过氧化物酶复合体法,通过抗ＭＭＰ３的单克隆抗体,对７８例椎间盘突出症和１４例非椎间盘突出症的椎间盘标本进行染色。结果：椎间盘突出症中的ＭＭＰ３比非椎间盘突出的多,差异非常显著。椎间盘突出症的临床分型：脱出型及游离型的ＭＭＰ３比凸出型的多,其差     

水通道蛋白1在不同程度退变腰椎间盘中的表达及意义

目的 观察水通道蛋白1在退变腰椎间盘组织中的表达变化,研究其与椎间盘退变的关系。方法 实验组取材于经手术治疗腰椎间盘突出症患者椎间盘标本30例,突出型、脱出型、游离型各10例;对照组取材于腰椎损伤致椎体骨折患者切除椎间盘10例。应用免疫组织化学法检测水通道蛋白1在椎间盘组织中的表达。结果 （1）苏木精-伊红染色显示,对照组椎间盘组织仍保持着致密的板层结构,实验组椎间盘组织多呈纤维化样改变。（2）各组髓核细胞中水通道蛋白1表达均明显高于同组纤维环细胞中的表达(P≤0.01)。（3）实验组突出型椎间盘标本髓核及纤维环细胞中水通道蛋白1表达明显低于对照组(P＜0.01),脱出型和游离型椎间盘标本中水通道蛋白1表达明显低于突出型 (P＜0.01)。结论 水通道蛋白1随着椎间盘突出、脱出、游离不同程度退变,表达呈逐渐下降趋势。     

腰椎间盘突出症血清MMP—3测定的意义

目的 进一步研究血清MMP－3的含量与腰椎间盘突出症发病的关系。方法 32例腰椎间盘突出症患者和10例正常人,用酶免疫法测定他们血清MMP－3的含量。结果 腰椎间盘突出症患者血清MMP－3含量的平均值为：35．57ng/ml,而正常人平均值为：27．56ng/ml,两者的差异有显著性意义（P＜0．01）。其中脱出型腰椎间盘突出症患者的血清MMP－3含量明显高于非脱出型患者（P＜0．05）。结论 血清MMP－3的测定可作为对腰椎间盘突出症的辅助诊断,并且证实血清MMP－3的含量与腰椎间盘的退变程度相关。     

环氧化酶2与血管内皮生长因子在突出腰椎间盘中的表达及意义

目的：探讨环氧化酶2（COX-2）、血管内皮生长因子（VEGF）在突出腰椎间盘中的表达及其意义。方法：62个突出椎间盘标本取自58例腰椎间盘突出症手术患者,包括突起型22个,破裂型20个,游离型20个。取材部位分别为突出组织或游离组织（A部位）和椎间隙残余髓核组织（B部位）。对照组取自4例新鲜年轻尸体的L3/4、L4/5及L5/S1椎间盘组织共12个标本,取材部位为椎间盘边缘（A部位）和中央髓核（B部位）;应用免疫组化法对各组标本中COX-2和VEGF的表达进行检测;应用图像分析系统测量标本中COX-2和VEGF表达量的平均光密度值。结果：在腰椎间盘突出组,特别是破裂型和游离型组的突出组织中存在富含新生血管的肉芽组织,COX-2和VEGF染色阳性细胞主要表达于肉芽组织中及突出组织的椎间盘细胞中,对照组未见阳性染色细胞。在突出组的A部位从突起型、破裂型到游离型COX-2和VEGF的表达均逐渐增高,差异有显著性（P〈0.01）。突出组的A部位COX-2和VEGF的表达明显高于B部位（P〈0.01）。腰椎间盘组织中COX-2和VEGF的表达存在明显相关性（r=0.855,P〈0.01）。结论：COX-2、VEGF参与腰椎间盘退变、突出的发病过程;随着腰椎间盘退变突出的进展,COX-2、VEGF的表达均逐渐增高;COX-2与VEGF表达密切相关。     

兔耳病理性瘢痕皮回植术后组织中基质金属蛋白酶－1及金属蛋白酶组织抑制剂－1表达的变化

目的通过建立兔耳模型观察基质金属蛋白酶－1（matrixmetalloproteinase－1,MMP－1）及金属蛋白酶组织抑制剂－1（tissueinh｜bitorofmetalloproteinase1,TIMP1）在病理性瘢痕皮回植术后组织中表达的变化,探讨瘢痕皮回植治疗病理性瘢痕的机制。方法建立兔耳病理性瘢痕模型。共分为3组：正常皮肤组（对照组,A组）、病理性瘢痕组（B组）及瘢痕皮回植组（c组）。切取标本行HE染色和Masson特殊组织化学染色及免疫组织化学染色,观察各组标本MMP－1、TIMP－1的表达情况。结果病理性瘢痕经瘢痕皮回植术后,MMP－1及TIMP－l均较A组明显升高（P〈O．01）．MMP一1的表达较TIMP一1明显增强（P〈O．01）。结论瘢痕皮回植术治疗瘢痕的机制与瘢痕组织内MMP一1和TIMP一1相互作用的失衡有关。     

整合素在人退变椎间盘髓核组织中的表达及意义

目的:观察整合素α1、α5、αv、β1、β3亚基在人退变椎间盘中的表达情况;探讨其在椎间盘退变中的意义.方法:术中收集人椎间盘髓核标本28个;其中6个来自6例脊柱骨折患者;设为对照组(n=6);22个来自20例椎间盘突出症患者;突出10个(突出组;n=10);脱出12个(脱出组;n=12).应用逆转录聚合酶链式反应(RT-PCR)和免疫沉淀技术测定整合素α1、α5、αv、β1、β3和整合素的配体——胶原蛋白(Ⅰ和Ⅱ型)、纤维结合蛋白在三组椎间盘髓核内的表达情况.结果:整合素α1、α5、αv、α1、α3在三组椎问盘髓核内都有表达;整合素α5在脱出组和突出组的表达分别是正常组的2.2倍和1.5倍;整合素β1在脱出组和突出组的表达分别是正常组的2.5倍和1.6倍;纤维结合蛋白的表达同样有升高的趋势.整合素α1、αv、β3在三组内的表达无统计学差异.结论:在退变的椎间盘髓核内整合素α5和β1亚基的表达增加;可能与椎间盘退变相关.     

细胞因子IL-1a、IL -6、TNF-a、MMP3与颈椎间盘退变机制的相关性研究

[目的]探讨细胞因子在颈椎间盘退变机制中的作用及其与神经功能的相关性.[方法]实验组椎间盘组织取自46例颈椎病患者,根据术前颈椎MRI及术中椎间盘突出情况分为两组:退变组(24例)和突出组(22例).对照组椎间盘组织取自15例无颈椎病病史的颈椎外伤患者.根据颈椎病患者术前JOA评分分为三组:轻度组(17例),中度组(15例)和重度组(14例).采用酶联免疫吸附法(ELISA法)分别检测不同退变程度颈椎间盘中IL-1a、IL -6、TNF -a和MMP3的表达水平.[结果]对照组、退变组和突出组三组之间比较,IL -1a、IL -6、TNF-a和MMP3的表达有统计学意义(P＜0.05),其表达水平与颈椎间盘退变呈正相关趋势;轻度组、中度组和重度组三组之间比较,MMP3、TNF -a的表达有统计学意义(P＜0.05),其表达水平与JOA评分呈负相关趋势.[结论]IL -1、IL -6、TNF -a和MMP3与颈椎间盘退变密切相关,其表达水平与椎间盘退变呈正相关趋势;TNF -a与神经功能有关,可能在神经损伤中起主导作用;MMP3与椎间盘突出有关,对TNF -a的神经功能损伤可能起促进作用.     

基质金属蛋白酶－9、细胞金属蛋白酶抑制因子－1在胃癌中的表达

目的：探讨基质金属蛋白酶－9（MMP－9）,组织金属蛋白酶抑制因子－1（TIMP－1）在胃癌中表达的意义。方法：采用免疫组化S－P法对47例胃癌组织进行MMP－9及TIMP－1的检测。结果：MMP－9,TIMP－1主要表达于癌周基质细胞,癌细胞少量表达,MMP－9,TIMP－1表达与胃癌患淋巴结转移（P＜0．01）,浆膜浸润相关（P＜0．01）;TIMP－1的表达与胃癌TNM分期相关（P＜0．05）,而MMP－9的表达与胃癌TNM分期无相关性（P＞0．05）。结论：MMP－9及TIMP－1可作为判断胃癌恶性行为的重要生物学标记物。     

MMP-2、MMP-9、TIMP-1在星形细胞瘤中的表达及其意义

目的：探讨基质金属蛋白酶（MMPs）中MMP－2、MMP－9及MMP－9的抑制剂TIMP－1在星形细胞瘤中表达的相互关系及其意义。方法：57例星形细胞瘤标本，其中I级星形细胞瘤11例，Ⅱ级星型细胞瘤16例，Ⅲ级星形细胞瘤17例，Ⅳ级星形细胞瘤13例。正常对照脑组织标本8例。计算平均阳性率。结果：低级别星形细胞瘤与高级别星形细胞瘤MMPs的表达差异有非常显著性（P＜0．01），而TIMPs的表达差异无显著性（P＞0．05）。结论：基质金属蛋白酶MMPs的表达与星形细胞瘤恶性程度密切相关。MMPs与TIMPs表达的平衡与星形细胞瘤恶性程度密切相关。     

膀胱癌中MMP-2、TIMP-2的表达及其与浅表性肿瘤复发的关系

目的：研究基质金属蛋白酶－2（MMP－2）和金属蛋白酶组织抑制因子－2（TIMP－2）在膀胱癌中的表达以及它们与肿瘤临床病理因素和复发的关系。方法：用免疫组织化学SP法检测46例膀胱移行细胞癌标本中MMP－2、TIMP－2的表达，并将它们与肿瘤临床和病理参数相比较。结果：在46例膀胱癌中，MMP－2、TIMP－2的阳性率分别为47.8%和58.7%，TIMP－2在间质中的表达率为47.8%。MMP－2表达率随着肿瘤理分级、临床分期的升高而增加，而TIMP－2表达率则呈下降趋势，但在浅表性膀胱癌（Ta-T1）中，TIMP－2的表达与MMP－2相似，随着肿瘤分期分级的升高而增加，TIMP－2间质表达阳性组中浅表性膀胱癌的2年复发率显著高于表达阴性组。结论：MMP－2和TIMP－2的相互作用对于膀胱癌的侵袭发展发挥了重要作用。TIMP－2在间质中表达可作为判断浅表性膀胱癌复发的预后指标。     

重度肩锁关节脱位的手术治疗

目的：对15例重度肩锁关节脱位的手术7治疗进行治疗,方法：15例全部为Allman分型中的Ⅲ型损伤,其中有11例切除纤维软骨盘,7例修复锁韧带,3例加用一枚松质骨螺钉固定于锁骨与喙空间,肩锁韧带全部修复,用两枚克氏针交叉固定于肩锁关节。结果：经10个月－6年的随访。疗效评价按Karlsson分类A级为12例,B级3例,病人均重返原工作岗位,有10例喙锁间隙软组织钙化,但对病人肩关节活动并无影响,结论：对重度肩锁关工锐位的病人应尽早手术治疗。克氏针交叉内固定是一种简单而有效的方法,纤维软骨盘是否切除和喙锁韧带是否修复对预后无明显影响。     

Histological development of intervertebral disc herniation

Sagittal and horizontal sections of 257 intervertebral discs obtained at autopsy and material obtained from 441 operations for herniation of a disc were examined histologically. In the material that was taken at autopsy, myxomatous degeneration of the annulus fibrosus increased in proportion to the age of the subject. The bundles in the internal layer of the annulus fibrosus reversed their usual direction and showed myxomatous degeneration, sometimes resulting in posterior and anterior convex bulging in the internal layer of the anterior and posterior parts of the annulus fibrosus, respectively. When material from a disc was surgically removed as a single free fragment (as in a complete extrusion or a sequestration type of herniation), annulus fibrosus with myxomatous degeneration was found in most material, while the nucleus pulposus rarely was. These results suggest that, from the standpoint of pathomechanism, a protrusion type of herniation of the annulus fibrosus exists in which only the annulus fibrosus is protruded due to reversal of the bundles of the annulus fibrosus, without involvement of the nucleus pulposus. This type of herniation would be a separate entity from the protrusion type of herniation of the nucleus pulposus that occurs when the nucleus pulposus is protruded through a fissure in the annulus fibrosus.     

Immunohistological study of intervertebral disc herniation of lumbar spine

In order to observe histological changes in the extruded and sequestrated intervertebral disc, we conducted pathological and immunological examinations of herniated disc materials taken at the time of discectomy. There were 49 disc materials (from 38 men and 10 women [aged 19 to 78 years; average, 36.6 years]). The herniation was classified into four types, based on the intraoperative observations: protrusion (P), subligamentous extrusion (SE), transligamentous extrusion (TE), and sequestration (S). There were 19 P type discs, 3 SE type, 10 TE type, and 17 S type. The surgical specimens were stained with hematoxylin-eosin, as well as immunohistological staining with the labelled streptavidin biotin method, using human T-cell , human B-cell, and human macrophage antibodies. Inflammatory-cell infiltration was observed at the border of the disc. These findings were present in 19 discs (70%) of the 27 discs of TE and S types (10 TE and 17 S types), but were not seen in the 22 discs of P and SE types (19 P and 3 SE types). Immunohistological staining of the area with inflammatory-cell infiltration revealed the presence of T cells and macrophages, which suggested that this cell infiltration originated from T cells and macrophages, and that the spontaneous resorption of the disc may have resulted from the phagocytic activities of these cells. Received for publication on June 1, 1998; accepted on Nov. 8, 1999     

Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica

Proinflammatory cytokines have been identified in herniated intervertebral discs in humans, and such cytokines have experimentally been demonstrated to be important in the pathophysiological mechanisms of disc herniation. Cerebrospinal fluid (CSF) and serum concentrations of interleukin (IL)-1beta IL-6, IL-8, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were investigated using the enzyme-linked immunosorbent assay (ELISA) technique in 39 patients with lumbar disc herniation and sciatica. Pain duration and pain intensity (visual analogue scale, VAS) were recorded at inclusion, and a clinical examination was performed evaluating neurological findings. The extent of disc herniation (protrusion or extrusion/sequestration) was evaluated perioperatively. Normal concentrations of IL-1beta, IL-6, IFN-gamma and TNF-alpha were present in CSF and serum in almost all patients with lumbar disc herniation. The concentrations of IL-8 in CSF were increased in 12 out of 39 patients, and these increased levels of IL-8 correlated to a short duration of pain and to more pronounced herniation (extrusion or sequestration). No relationship between IL-8 concentrations in CSF and pain intensity, positive neurological findings or a positive straight leg-raising (SLR) test was found. The observation of increased concentrations of IL-8 in CSF in patients with a short duration of symptoms supports the concept of the initial involvement of inflammatory mechanisms after a disc herniation. The finding that most of the patients with increased concentrations of IL-8 in CSF had an extrusion or a sequestration may suggest that the increase in IL-8 is related to mechanical nerve root compression, but may also indicate a biochemical effect exerted by the herniated disc on the surrounding tissue. Further studies on the potential role of IL-8 as a biomarker for disc herniation are warranted.     

前列腺素E2在突出腰椎间盘中的表达及其与坐骨神经痛的关系

目的探讨前列腺素(PG)E2在突出腰椎间盘组织中的表达及其在坐骨神经痛发病机制中的作用。方法 42个突出椎间盘标本取自42例腰椎间盘突出并有坐骨神经放射性疼痛症状的手术治疗患者,其中膨隆型12例,破裂型15例,游离型15例,取材部位为紧贴神经根突入椎管的椎间盘组织(A部位)和椎间隙内残存的椎间盘组织(B部位)。术前采用视觉模拟评分(VAS)对所有患者坐骨神经痛严重程度进行评分。应用酶联免疫吸附试验(ELISA)检测PGE2含量。结果 A部位PGE2含量自膨隆型、破裂型至游离型逐渐升高,差异有显著性(P<0.01);A部位PGE2含量高于B部位(P<0.01);PGE2含量与患者坐骨神经痛VAS评分存在明显相关性(r=0.848,P<0.01)。结论 PGE2参与了腰椎间盘退变、突出的发病机制,PGE2含量与坐骨神经痛程度呈正相关性。     

腰椎间盘中血管内皮生长因子的表达及其意义

目的 :观察并探讨腰椎间盘中内源性血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)的表达分布规律及其意义。方法 :采用免疫组织化学技术检测 1 6例胎儿期、8例生长期、1 2例成熟退变期和 42例突出椎间盘中VEGF的表达。结果 :胎儿椎间盘脊索细胞和纤维环外层血管内皮细胞出现阳性免疫染色 ,阳性率为 87 5 % ;生长期和成人期椎间盘未见阳性表达 ;退变突出组总阳性率为 83 3 %。VEGF表达主要出现于破裂型和游离型椎间盘突出 (P <0 0 1 ) ,其细胞来源主要是突出椎间盘组织中毛细血管内皮细胞、髓核内的类软骨细胞及单核巨噬细胞。年龄与VEGF表达阳性率关系不大 (P >0 0 5)。病程超过 1年者VEGF阳性率明显低于 1年以内者 (P <0 0 5)。结论 :胎儿期和破裂型 (包括游离型 )突出椎间盘组织可产生内源性VEGF ,突出椎间盘中VEGF的阳性表达与病程、突出类型密切相关     

A New Pathological Classification of Lumbar Disc Protrusion and Its Clinical Significance

Lumbar disc protrusion is common. Its clinical manifestations and treatments are closely related to the pathological changes; however, the pathological classification of lumbar disc protrusion is controversial. This article introduces a new pathological classification comprising four types of lumbar disc protrusion according to intraoperative findings. The damage‐herniation type is probably caused by injury and is characterized by soft herniation, the capsule can easily be cut and the broken disc tissue blocks overflow or is easily removed. The broken disc substances should be completely removed; satisfactory results can be achieved by minimally invasive endoscopic surgery. The degeneration‐protrusion type is characterized by hard and tough protrusions and the pathological process by degeneration and proliferative reaction. The nerve should be decompressed and relaxed with minimally invasive removal of the posterior wall; the bulged or protruded disc often need not be excised. The posterior vertebral osteochondrosis with disc protrusion type is characterized by deformity of the posterior vertebral body, osteochondral nodules and intervertebral disc protrusion. The herniated and fragmented disc tissue should be removed with partially protruding osteochondral nodules. Intervertebral disc cyst is of uncertain pathogenesis and is characterized by a cyst that communicates with the disc. Resection of the cyst under microscopic or endoscopic control can achieve good results; and whether the affected disc needs to be simultaneously resected is controversial. The new pathological classification proposed here is will aid better understanding of pathological changes and pathogenesis of lumbar disc protrusion and provides a reference for diagnosis and treatment.     

Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological findings in 500 en bloc surgical samples. Laboratory investigation

OBJECT: In this paper the authors' goal was to identify histological and immunohistochemical differences between cervical disc hemrniation and spondylosis. METHODS: A total of 500 cervical intervertebral discs were excised from 364 patients: 198 patients with disc herniation and 166 patients with spondylosis. We examined en bloc samples of endplate-ligament-disc complexes. Types of herniation and graded degrees of disc degeneration on MR images were examined histologically and immunohistochemically. RESULTS: The herniated discs showed granulation tissue, newly developed blood vessels, and massive infiltration of CD68-positive macrophages, which surrounded the herniated tissue mainly in the ruptured outer layer of the anulus fibrosus. The vascular invasion was most significant in uncontained (extruded)-type herniated discs. Chondrocytes positive for matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-alpha, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were abundant in both herniated and spondylotic discs. Free nerve fibers, positive for nerve growth factor (NGF), neurofilament 68, growth-associated protein (GAP)-43, and substance P, were strongly apparent in and around the outer layer of uncontained (extruded)-type herniated discs, with enhanced expression of NGF. The authors observed that herniated discs showed more advanced degeneration in the outer layer of the anulus fibrosus around the granulation tissue than spondylotic discs. On the other hand, spondylotic discs showed more advanced degeneration in the cartilaginous endplate and inner layer of the anulus fibrosus than herniated discs. Spondylotic discs also had thicker bony endplates and expressed TNFalpha and MMP-3 more diffusely than herniated discs, especially in the inner layer of the anulus fibrosus. CONCLUSIONS: The authors' results indicate that herniated and spondylotic intervertebral discs undergo different degenerative processes. It is likely that TNFa, MMP-3, bFGF, and VEGF expression is upregulated via the herniated mass in the herniated intervertebral discs, but by nutritional impairment in the spondylotic discs. Macrophage accumulation around newly formed blood vessels in the herniated disc tissues seemed to be regulated by MMP-3 and TNFalpha expression, and both herniated and spondylotic discs exhibited marked neoangiogenesis associated with increased bFGF and VEGF expression. Nerve fibers were associated with NGF overexpression in the outer layer of the anulus fibrosus as well as in endothelial cells of the small blood vessels.