退变颈椎间盘中IL-17表达与分布的研究

目的 观察退变颈椎间盘中自细胞介素-17(IL-17)的表达与分布,并探讨其与颈椎间盘退变发生发展的关系.方法 实时荧光相对定量PCR(RQ-PCR)检测30例退变颈椎间盘及10例正常对照椎间盘中IL-1β、IL-17、肿瘤坏死因子-α(TNF-α)和孤核受体(retinoid-related orphan re-ce...     

颈椎间盘退变中血管浸润现象的研究

目的探讨颈椎间盘退变中血管浸润现象的规律。方法34例病人均来自本院骨科的需手术治疗的住院病人,其中脊髓型颈椎病16例,单纯颈椎间盘突出症18例,所有病人术前均行MRI以判定颈椎间盘退变的分级,术后椎间盘标本常规脱水、浸蜡、包埋,制作蜡块。常规切片,HE染色,普通光镜下观察血管浸润现象。结果在57个椎间盘标本中,共检出21例有血管浸润,其中颈椎间盘突出症中共检出13个有血管浸润的椎间盘,脊髓型颈椎病共检出8个有血管浸润的椎间盘。病程在5个月以内或MRI分级为Ⅰ级和Ⅱ级的患者其椎间盘血管浸润率高。结论单纯颈椎间盘突出症患者其椎间盘血管浸润率高于脊髓型颈椎病患者。血管浸润大多出现于病程及椎间盘退变早期,是椎间盘自身修复的一种方式。     

青年颈椎病手术患者人群特征及其与颈椎间盘退变的相关性

目的:分析青年颈椎病手术患者的人群特点及其与颈椎间盘退变(cervical disc degeneration,CDD)程度之间的关系.方法:回顾性收集2010年9月～2020年9月在宁波市第六医院因颈椎病行手术治疗且年龄为18-40周岁的患者资料.统计患者性别、年龄、体质指数(body mass index,BMI)...     

抗骨增生胶囊、葡立胶囊对退变颈椎间盘蛋白多糖、IL-1a的影响

目的: 研究抗骨增生胶囊、葡立胶囊对退变颈椎间盘蛋白多糖、IL 1a含量代谢的影响。方法: 30只新西兰大白兔随机分为对照组、浅层造模组、全层造模组、浅层治疗组、全层治疗组, 每组 6只。按照施杞的方法造模 6个月, X线片证实退变后喂服抗骨增生胶囊(1. 1g·kg-1 ) 和葡立胶囊 (0. 06g·kg-1 ) 1个月。观察治疗前后椎间盘内蛋白多糖、IL 1a含量的变化。结果: 造模组椎间盘内蛋白多糖含量减少, IL 1a含量增加且与对照组相比有显著差异。而治疗组椎间盘蛋白多糖含量增加, IL 1a含量减少, 与造模组相比有显著差异, 与对照组相比无显著差异。结论: 抗骨增生胶囊与葡立胶囊联合应用, 能够抑制炎症因子IL 1a的产生, 促进椎间盘内蛋白多糖的合成, 延缓颈椎间盘的退变进程。     

突出颈椎间盘组织炎症反应机制的研究

目的:研究颈椎病发生中突出颈椎间盘组织的炎症反应机制,探讨炎症反应在颈椎间盘退变和颈椎病发病中的作用.方法:临床收集了31个脊髓型颈椎病病人的35个突出的颈椎间盘标本和3个成年人的7个正常颈椎间盘标本.将每个标本分为2份,1份作组织学检查,观察有无炎细胞浸润,1份用生物化学方法测定其中IL-1α,IL-6和TNF-α三种细胞因子含量.结果:35例突出颈间盘中,18例(51.4%)在边缘区域有大量炎细胞浸润,其余17例(48.6%)未见炎细胞浸润,对照组也未见炎细胞浸润.生物化学测定结果表明,突出颈间盘组织中IL-1α,IL-6和TNF-α三种细胞因子含量明显高于正常对照组.炎细胞浸润组与无炎细胞浸润组三种细胞因子含量相当,在统计学上无任何差异.结论:突出颈间盘组织具有炎症反应特性,炎症反应可能在颈椎间盘退变和颈椎病的发生发展中起重要作用.     

炎性因子TNF—α及IL-18与椎间盘退变的相关性研究

[目的]通过测定TNF-α及IL-18在正常组与实验组椎间盘组织中的表达,探讨在椎间盘退变中的作用,进一步了解椎间盘退变的发生机制.[方法]收集新疆石河子大学医学院第一附属医院骨科椎间盘突出症患者术后椎间盘病理组织34例用于实验组,年龄27～69岁,平均年龄46.24±11.25岁;取脊柱骨折外伤术后椎间盘组织标本7例,并取石河子大学医学院病理科尸检椎间盘标本8例,共15例用于对照组,年龄25～52岁,平均年龄40.07±8.43岁.采用免疫组化法和ELISA两种方法进行检测.[结果]光镜下观察,免疫组化检测TNF-α、IL-18蛋白表达阳性细胞表现为细胞浆中出现棕黄色、褐色或浅棕黄色染色,结果判定及统计学分析后表明:实验组TNF-α蛋白表达高于对照组,差异有统计学意义(P＜0.01),实验组IL-18蛋白表达高于对照组,差异有统计学意义(P＜0.01).Elisa法证实实验组中TNF-α含量为82.18±21.91 ng/ml,IL-18的含量为45.39±21.23 ng/ml;对照组中TNF-α含量为8.68±0.78 ng/ml、IL-18含量为3.58±2.84 ng/ml.两者差异均有统计学意义(P<0.01),且两种细胞因子的表达均与患者年龄及病程呈正相关.[结论]椎间盘组织中细胞因子TNF-α及IL-18表达与椎间盘退变有关,推测可能是导致椎间盘组织退变的重要原因之一.     

年轻颈痛患者颈椎弧度与颈椎间盘膨隆程度的相关性研究

目的:探讨颈椎弧度与年轻颈痛患者颈椎间盘膨隆程度的相关性.方法:回顾性分析2015年1月至2018年12月收治的539例年轻颈痛患者,其中男251例,女288例,年龄18～40(32.2±6.3)岁.通过颈椎X线和MRI检查测量患者的颈椎弧度和颈椎膨隆程度,并根据颈椎弧度将患者分为颈椎前凸组(颈椎弧度＞7 mm)175...     

人工颈椎间盘置换术治疗C_(3-4)椎间盘突出症的中期疗效研究

目的探讨人工颈椎间盘置换术(artificial cervical disc replacement,ACDR)治疗C_(3-4)椎间盘突出症的中期临床及影像学结果。方法 2010年4月-2014年12月,我院采用ACDR治疗C_(3-4)椎间盘突出症患者9例,含C_(3-4)的双节段椎间盘突出症患者12例;使用Prestige LP人工椎间盘16例,使用Discover人工椎间盘5例;男14例,女7例;年龄35-60岁,平均42.8岁;其中神经根型颈椎病8例,脊髓型7例,混合型6例;术前病程12-60个月,平均27.6个月。分别在术前、术后1周及末次随访时采用生活质量量表(SF-36)、日本矫形外科协会(JOA)脊髓功能评分及颈椎功能障碍指数(NDI)评估临床疗效,在颈椎正侧位X线片上观察假体稳定性并测量C_(3-4)脊柱功能单位(functional spinal unit,FSU)的前凸角,在过伸过屈位X线片上测量C_(3-4)节段屈伸活动度。结果 21例患者术后均获得随访,随访时间6-48个月,平均28.3个月。所有患者术后神经症状均明显改善,SF-36躯体及心理评分、JOA及NDI评分术后1周及末次随访时均明显优于术前(P0.05)。置入的假体均保留了活动度,无假体沉降或移位。C_(3-4)节段FSU的前凸角与术前相比差异无统计学意义(P0.05),术后1周时C_(3-4)节段屈伸活动度较术前明显下降(P0.05),末次随访时恢复到术前水平(P0.05)。术后4例患者出现咽部不适,2例患者出现C_(3-4)节段周围的异位骨化。结论 C_(3-4)节段人工颈椎间盘置换术后中期临床效果良好,维持了手术节段的生理曲度,且人工椎间盘在C_(3-4)节段仍能保持较好的活动度。     

炎性因子IL-1β、TNF-α与椎间盘退变关系的研究进展

IL-1β与TNF-α炎性因子作为椎间盘退变过程中的重要参与者日益受到国内外学者的关注。在椎间盘退变并最终导致下腰痛及神经根性症状全过程中,炎性因子从中起到重要的作用。在机械创伤、过度负荷、基因易感及感染等因素的作用下,纤维环及髓核细胞合成TNF-α、IL-1β。这些炎性因子在椎间盘退变过程中的作用大致可分为3个阶段。目前关于炎性因子在椎间盘退变病理生理过程中确切的调控机制仍需进一步研究,重点将在于阐述炎性因子在椎间盘退变中的调控机制、椎间盘退变的分子靶向治疗、细胞信号通路干预及寻找抗炎治疗的最佳时机上,为其将来的临床应用提供依据。     

椎间盘退变与终板内微血管形态改变的相关性研究

目的:通过观测大白兔椎间盘退变过程中椎间盘终板内的血管形态以及血流量的改变,探讨终板内微血管的改变与椎间盘退变之间的相关性.方法:选用40只新西兰大白兔随机分为2组,通过切除造模组20只免腰椎棘间、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.分别在术后4、8个月通过扫描电镜、血流激光多普勒仪测定椎体终板内的血管形态以及血流量.结果:在椎间盘退变过程中,椎间盘终板内的血管芽形态逐渐被破坏,微血管数量相应减少,终板内的血流量也明显减少,同时终板内血流量中心部位(靠近髓核区域)血流量多于终板内周围区域的血流量.结论:椎体终板内微血管的改变可能是椎间盘退变的促进因素.     

Fas ligand plays an important role for the production of pro‐inflammatory cytokines in intervertebral disc nucleus pulposus cells

It is suggested that pro‐inflammatory cytokines, which are produced by interaction of the intervertebral nucleus pulposus cells and macrophages, may be linked to the cause of pain of the intervertebral disc herniation. This study carries out the in vitro experiments to examine the mechanism, with the use of the co‐culture of an immortalized cell line of nucleus pulposus of the human intervertebral disc and the macrophage cell line. As a result, it is found that the production of pro‐inflammatory cytokines is significantly larger at the co‐culture group than at the independent culture group. Also, at the co‐culture group of macrophages and intervertebral nucleus pulposus cells with over‐expression of fas ligand (FasL), the production of pro‐inflammatory cytokines is found to be far larger. Furthermore, it is found that these pro‐inflammatory cytokines are produced mainly by the intervertebral nucleus pulposus cells with over‐expression of FasL, and that the expression of a disintegrin and metalloproteinase (ADAM) 10, which controls the expression of FasL and activates reverse signaling inside cells, also increases. From these findings, it is suggested that FasL and ADAM10 play an important role in the production of pro‐inflammatory cytokines coming from interaction of the intervertebral nucleus pulposus cells and macrophages. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 608–615, 2013     

Interleukin‐1β induces angiogenesis and innervation in human intervertebral disc degeneration

Degenerative disorders of the intervertebral discs (IVDs) are generally characterized by enhanced matrix degradation, angiogenesis, innervation, and increased expression of catabolic cytokines. In this study, we investigated the effects of inflammatory cytokines, IL‐1β, and TNF‐α, on the expression of an angiogenic factor, vascular endothelial growth factor (VEGF), and neurotrophic factors, nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF), in human IVD degeneration. IL‐1β and TNF‐α stimulated the gene expression of VEGF, NGF, and BDNF in nucleus pulposus (NP) cells isolated from patient tissues. Immunohistochemical results demonstrated a positive correlation between IL‐1β and VEGF/NGF/BDNF expression in human IVD tissues. RNA expression analysis of patient tissues also identified positive correlations between VEGF and platelet endothelial cell adhesion molecule‐1 (PECAM‐1) and between NGF/BDNF and protein gene product 9.5 (PGP9.5). Our findings suggest that IL‐1β is generated during IVD degeneration, which stimulates the expression of VEGF, NGF, and BDNF, resulting in angiogenesis and innervation. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:265–269, 2011     

Is there any relationship between proinflammatory mediator levels in disc material and myelopathy with cervical disc herniation and spondylosis? A non-randomized,prospective clinical study

The proinflammatory mediator (PIM) levels were assessed in surgically removed samples of herniated cervical intervertebral discs. The objective of this study was to investigate if there is a correlation between the levels of PIMs in disc material and myelopathy associated with cervical intervertebral disc herniation and spondylosis. The role of proinflammatory mediators in the degeneration of intervertebral disc and the inflammatory effects of disc herniations on radicular pain has been previously published. However, the possible relationship between PIMs and myelopathy related to cervical disc herniation and spondylosis has not been investigated before. Thirty-two patients undergoing surgery for cervical disc herniation and spondylosis were investigated. Surgically obtained disc materials, stored at 70 degrees C, were classified into two groups: cervical disc herniation alone or with myelopathy. Biochemical preparation and solid phase enzyme amplified sensitivity immunoassay (ELISIA) analysis of the samples were performed to assess the concentration of mediators in the samples. Very similar values of interleukin-6 were found in both groups whereas the concentrations of mediators were significantly higher in myelopathy group. This study has demonstrated that PIMs are involved in cervical intervertebral disc degeneration with higher concentrations in the samples associated with myelopathy.     

Interleukin‐6 and interleukin‐6 receptor expression,localization, and involvement in pain‐sensing neuron activation in a mouse intervertebral disc injury model

The pathological mechanism of intractable low back pain is unclear. However, intervertebral disc (IVD) degeneration is a primary cause of low back pain, and pain‐related mediators, such as interleukin‐6 (IL‐6), have been correlated with discogenic pain. The objective of this study is to elucidate the mechanism of local IL‐6 and IL‐6 receptor (IL‐6R) expression after IVD injury as well as determine the involvement of IL‐6/IL‐6 signaling in discogenic pain. To do this, quantitative and immunohistological analyses in a mouse model of IVD injury were performed. Firstly, we measured the local expression levels of IL‐6 and IL‐6R in IVDs by enzyme‐linked immunosorbent assay (ELISA). Secondly, we immunohistochemically confirmed their localization in injured IVDs. Lastly, we evaluated the effects of intradiscal injection of an IL‐6 inhibitor by evaluating pain‐related protein, calcitonin gene‐related peptide (CGRP), expression in dorsal root ganglia (DRG) neurons that innervate IVDs. Injured IVDs showed increased production of IL‐6 and IL‐6R. IL‐6 and IL‐6R expression in the injured IVD were predominantly localized in the annulus fibrosus and endplate, and intradiscal injection of the IL‐6 inhibitor suppressed CGRP expression in the DRG neurons. These results show that IL‐6 and IL‐6R expression levels are responsive to IVD injury and that inhibition of IL‐6/IL‐6R signaling may be a promising analgesic treatment for degenerative disc diseases. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1508–1514, 2015.