黄韧带肥厚与腰椎管狭窄症关系的病理学研究

A Pathologic Study on the Hypertrophy of Lumbar Ligamentum Flavum and Its Relationship to Lumbar Spinal Stenosis

目的通过病理学研究探讨腰椎黄韧带变性、肥厚的病因及其与腰椎管狭窄症的关系。方法黄韧带组织取材于腰椎管狭窄症患者及腰椎间盘突出症患者。选取切片分别用费尔赫夫(Verhoeff)染色及免疫组化染色。结果 (1)Verhoeff染色:光镜下所见:腰椎管狭窄症组:①弹力纤维明显减少、断裂;②大面积胶原纤维增生区域,而在黄韧带的边缘区域胶原纤维增生尤为明显。(2)腰椎管狭窄症组与椎间盘突出症组患者黄韧带中胶原纤维与弹力纤维比值间差异有统计学意义(P<0.01);两组患者黄韧带中白介素-6(IL-6)、转化生长因子-β1(TGF-β1)、肿瘤坏死因子-α(TNF-α)阳性表达程度比较,差异均有统计学意义(P<0.01)。结论 (1)黄韧带变性肥厚在椎管狭窄症患者的病理表现具有特征性——①黄韧带中的胶原纤维增生,特别是在黄韧带的边缘区域增生尤为明显,且排列不规则;②弹力纤维明显减少且有断裂;③纤维细胞数量减少,而成纤维细胞数量增生明显,成纤维细胞向软骨细胞过渡区域扩大;④出现灶性钙化;⑤血管数目增多,个别有炎性细胞浸润。(2)IL-6、TGF-β1、TNF-α3种炎性因子在椎管狭窄症肥厚黄韧带中的表达呈相对一致性,约80%明显增高。黄韧带变性、增殖、肥厚,也是无菌性炎性因子作用的结果。

Objective To study the etiology of the degenerative and hypertrophied lumbar ligamentum flavum and its relationship to lumbar spinal stenosis.Methods Ligamentum flavum specimens were obtained at operation from a total of 25 cases of LSS,25 cases of lumbar disc herniation and 6 cases of spinal fractures.These slices were selected for Verhoeff staining and immunohistochemistry staining.The collagen relative contents（the ratio of collagen fiber to elastic fiber） were measured by image analysis system,which was used to detect the pathologic change of collagen fiber and elastic fiber by Verhoeff staining.The results of measurement were compared between LSS and LDH group.With immunohistology stain,the expression of the three cytokines-TGF-β1,TNF-αand IL-6 were observed and compared between LSS and LDH,which was used to research the etiology of HLF from the biochemical level.Results（1）Verhoeff Stain：LSS group：①Elastic fibers were irregularly arranged,ruptured,swollen and few in number.②The number of collagen fibers was obviously increased,especially in proximity to the laminal insertion.（2）Comparing the ratio of collagen fibers and elastic fibers in ligamentum flavum of LSS and LDH group,the difference was statistically significant（P0.01）;Comparing the degree of positive expression of TGF-β1,TNF-αand IL-6 in ligamentum flavum of LSS and LDH group,the difference was statistically significant（P0.01）.Conclusion（1） The pathological representation of degeneration and hypertrophy of LF is of characterization.①The number of collagen fibers was obviously increased,especially in proximity to the laminal insertion.②Elastic fibers were irregularly arranged,ruptured,swollen and few in number.③Fibrocytes were fewer and fibroblasts were more numerous than normal.The fibrocartilaginous zone near the bone insertion underwent enlargement.④Areas of calcification were often seen in the ligamentous tissue of stenotic patients,particularly the most elderly ones.⑤Blood vessels had increased in numbers and inflammatory cells were observed occasionally.（2） In the course of degeneration of LF,we observed that anti-inflammatory cytokines and inflammatory cytokines had gradually increased.Sterile inflammatory cytokines also lead to the degeneration,proliferation and hypertrophy of lumbar LF.