Zhang Kai, Sun Wei, Liu Xin-Yu, Zhao Chang-Qing, Li Hua, Sun Xiao-Jiang, You-Zhuan Xie, Ding Wei, Zhao Jie
*Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai †Department of Orthopedic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, PR China.
Clin Spine Surg. 2017 Apr;30(3):E189-E191. doi: 10.1097/BSD.0000000000000048.
Histologic, immunohistochemical (IHC), and enzyme-linked immunosorbent assay analysis of the human ligamentum flavum (LF).
The purpose of this study was to determine the level of expression of lysophosphatidic acid (LPA) in the LF from lumbar spinal stenosis (LSS) patients and to analyze the relationship among LPA, LPA receptors (LPARs), and LF hypertrophy.
LF hypertrophy and fibrosis are important causes of LSS. LPA is involved in the fibrotic process in multiple organ systems. Therefore, we hypothesized that LPA and its receptors might also play a role in degeneration of the LF in LSS patients.
Forty-one LF samples were enrolled in this study. The thickness of the LF was measured by magnetic resonance imaging. Histologic analysis using hematoxylin and eosin and Masson trichrome stain was performed for each LF to evaluate the architecture of the extracellular matrix. The content of LPA and connective tissue growth factor (CTGF) in LF samples was analyzed using enzyme-linked immunosorbent assay. The expression of LPAR1 was determined by IHC.
Degeneration of the LF was characterized by an increase in disorganized elastic fibers and fibrotic transformation by extracellular collagen deposition. The thickness of the LF and the concentration of LPA and CTGF in the hypertrophic LF group were significantly higher than the control group. Furthermore, the LPA and CTGF concentrations had a positive correlation with the LF thickness (r=0.91, P<0.001 and r=0.943, P<0.001, respectively). On the basis of IHC analysis, the expression of LPAR1 was increased in the hypertrophy group.
The increased expression of LPA and LPAR1 is associated with the fibrosis and hypertrophy of the LF in patients with LSS. Further study on the mechanism underlying LF fibrosis may lead to new therapies for LF hypertrophy and fibrosis.
对人黄韧带（LF）进行组织学、免疫组织化学（IHC）和酶联免疫吸附测定分析。
本研究旨在确定腰椎管狭窄症（LSS）患者黄韧带中溶血磷脂酸（LPA）的表达水平，并分析LPA、LPA受体（LPARs）与黄韧带肥厚之间的关系。
黄韧带肥厚和纤维化是腰椎管狭窄症的重要病因。LPA参与多个器官系统的纤维化过程。因此，我们推测LPA及其受体可能也在LSS患者黄韧带退变中起作用。
本研究纳入41份黄韧带样本。通过磁共振成像测量黄韧带厚度。对每个黄韧带样本进行苏木精-伊红染色和Masson三色染色的组织学分析，以评估细胞外基质的结构。采用酶联免疫吸附测定法分析黄韧带样本中LPA和结缔组织生长因子（CTGF）的含量。通过免疫组织化学法测定LPAR1的表达。
黄韧带退变的特征是弹性纤维排列紊乱增加以及细胞外胶原沉积导致的纤维化转变。肥厚型黄韧带组的黄韧带厚度、LPA和CTGF浓度显著高于对照组。此外，LPA和CTGF浓度与黄韧带厚度呈正相关（r分别为0.91，P<0.001和r为0.943，P<0.001）。基于免疫组织化学分析，肥大组中LPAR1的表达增加。
LPA和LPAR1表达增加与LSS患者黄韧带的纤维化和肥厚有关。对黄韧带纤维化潜在机制的进一步研究可能会带来针对黄韧带肥厚和纤维化的新疗法。
