Lumbar ligamentum flavum hypertrophy is due to accumulation of inflammation-related scar tissue
Lumbar ligamentum flavum hypertrophy is due to accumulation of inflammation-related scar tissue
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DOI：
10.1097/01.brs.0000263407.25009.6e
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发表时间：
2007-05-15
期刊：
影响因子：
3
通讯作者：
Mohan, Suneeth E.
中科院分区：
文献类型：
--
作者：
Sairyo, Koichi;Biyani, Ashok;Mohan, Suneeth E.
研究设计.一个组织学，生物学和免疫组织化学评估使用人类样本的腰椎黄韧带。为了证实我们的假设，即黄韧带肥大是由炎症相关瘢痕组织的积累引起的。背景资料概要。腰椎管狭窄症是老年人最常见的脊柱疾病之一。椎管狭窄部分是由于黄韧带肥大所致。肥大机制尚不清楚。根据我们的初步分析，我们以前提出，肥大可能是由于积累的疤痕组织在韧带。有报道称炎症后会形成瘢痕组织;然而，包括我们之前的研究在内，还没有关于黄韧带炎症的报道。有必要对黄韧带炎症和瘢痕形成之间的关系进行深入研究。如果炎症与肥大有关，我们可以通过抑制炎症来控制/延缓肥大。获得21个黄韧带样本用于组织学研究。三色和Verhoeff-van Gieson染色分别用于评估纤维化（瘢痕形成）的程度和弹性纤维的含量。两个黄韧带样本，肥大和薄的控制韧带，用于全球基因评估寡核苷酸基因芯片技术。应用实时荧光定量逆转录聚合酶链反应技术检测16例黄韧带标本中环氧合酶（考克斯）-2信使核糖核酸的表达。免疫组化检测黄韧带中考克斯-2的表达。在肥大的黄韧带中，在整个黄韧带区域观察到严重的纤维化（瘢痕形成），并且瘢痕形成的严重程度与黄韧带厚度呈显著（r = 0.79; P < 0.0001）和正线性相关。基因阵列结果显示，在薄/对照和肥大韧带中，炎症相关基因如考克斯-2、肿瘤坏死因子-α和白细胞介素-1，6，8和15均表达。实时定量聚合酶链反应显示考克斯-2信使核糖核酸在所有黄韧带样本中表达。其表达与韧带厚度呈弱正相关。免疫组化显示黄韧带血管内皮细胞有考克斯-2的表达。纤维化（瘢痕形成）的积累导致黄韧带肥大。在黄韧带中发现炎症相关基因表达。结论：应用抗抑郁药预防黄韧带肥厚是可行的。
Study Design. A histologic, biologic, and immunohistochemical assessment using human samples of the lumbar ligamentum flavum.Objective. To prove our hypothesis that hypertrophy of the ligamentum flavum is caused by accumulation of inflammation-related scar tissue.Summary of Background Data. Lumbar spinal canal stenosis is 1 of the most common spinal disorders in elderly patients. Canal narrowing, in part, results from hypertrophy of the ligamentum flavum. The hypertrophy mechanism remains unclear. Based on our preliminary analyses, we have previously proposed that the hypertrophy may be due to accumulation of scar tissue in the ligament. Scar tissue is reported to develop after inflammation; however, there is no report, including our previous study, on inflammation in the ligamentum flavum. There is a need for an in-depth investigation of any relationship between inflammation and scar formation in the ligamentum flavum. If inflammation is related to hypertrophy, we may control/delay the hypertrophy by inhibiting the inflammation.Methods. Twenty-one ligamentum flavum samples were obtained for the histologic study. Trichrome and Verhoeff-van Gieson stains were used to assess the degree of fibrosis (scarring) and content of elastic fibers, respectively. Two ligamentum flavum samples, hypertrophied and thin control ligaments, were used for a global genetic assessment by oligonucleotide gene array technology with gene chips. Messenger ribonucleic acid expression of cyclooxygenase (COX)-2 was quantitatively measured from 16 ligamentum flavum samples using real-time reverse transcriptase polymerase chain reaction. Immunohistochemistry evaluated the cellular location of COX-2 in ligamentum flavum.Results. In the hypertrophied ligament, severe fibrosis (scarring) was observed in the entire area of the ligamentum flavum, and the severity of scarring showed a significant (r = 0.79; P < 0.0001) and positive linear correlation with ligamentum flavum thickness. Gene array results showed in both thin/control and hypertrophied ligaments expression of inflammation-related genes such as COX-2, tumor necrosis factor-alpha, and interleukin-1, 6, 8, and 15. Real-time polymerase chain reaction showed COX-2 messenger ribonucleic acid expression in all ligamentum flavum samples. Its expression showed weak positive linear correlation with the thickness of ligament. COX-2 was released from vascular endothelial cells in ligamentum flavum as per the immunohistochemical analysis.Conclusions. Accumulation of fibrosis (scarring) causes hypertrophy of the ligamentum flavum. Inflammation-related gene expression is found in the ligamentum flavum. It might be possible to prevent the hypertrophy of ligamentum flavum with antiinflammatory drugs.