Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Spine (Phila Pa 1976). 2021 May 1;46(9):E520-E527. doi: 10.1097/BRS.0000000000003832.
Experimental animal study.
The aim of this study was to clarify chronological effects of mechanical stress on ligamentum flavum (LF) using a long-term fusion rabbit model.
LF hypertrophy is a major pathology of lumbar spinal stenosis (LSS), but its mechanism remains unclear. We previously demonstrated mechanical-stress-induced LF hypertrophy with a rabbit model. However, we only investigated LFs at a single time point in the short-term; the effects of long-term mechanical stress have not been elucidated.
Eighteen-week-old male New Zealand White rabbits were randomly divided into two groups: the mechanical stress group underwent L2-3 and L4-5 posterolateral fusion and resection of the L3-4 supraspinal muscle, whereas the control group underwent only surgical exposure. Rabbits were sacrificed 16 and 52 weeks after the procedure. Axial specimens of LFs at L3-4 were evaluated histologically. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) was performed to assess the numbers of vessels and myofibroblasts.
In the mechanical stress group, LFs at the L3-4 level exhibited hypertrophy with elastic fiber disruption and cartilage matrix production at 16 and 52 weeks. A trend test indicated that mechanical stress induced LF hypertrophy, elastic fiber disruption, and cartilage matrix production in a time-dependent manner, with the lowest levels before treatment and the highest at 52 weeks. Immunostaining for α-SMA showed similar numbers of vessels in both groups, whereas the percentage of myofibroblasts was significantly larger at 16 and 52 weeks in the mechanical stress group than in the control group.
We demonstrated that long-term mechanical stress caused LF hypertrophy with progressive elastic fiber disruption and cartilage matrix production accompanied by enhanced myofibroblasts. In addition, the reported rabbit model could be extended to elucidate the mechanism of LF hypertrophy and to develop new therapeutic strategies for LSS by preventing LF hypertrophy.Level of Evidence: SSSSS.
实验动物研究。
本研究旨在使用长期融合兔模型阐明机械应力对黄韧带（LF）的时间效应。
LF 肥大是腰椎管狭窄症（LSS）的主要病理学表现，但其机制尚不清楚。我们之前使用兔模型证明了机械应激引起的 LF 肥大。然而，我们仅在短期研究中研究了 LF 的单一时间点；长期机械应力的影响尚未阐明。
18 周龄雄性新西兰白兔随机分为两组：机械应力组行 L2-3 和 L4-5 后路融合及 L3-4 棘上肌切除，对照组仅行手术暴露。术后 16 周和 52 周处死兔子。评估 L3-4 处 LF 的轴向标本的组织学表现。进行α-平滑肌肌动蛋白（α-SMA）免疫组织化学染色以评估血管和肌成纤维细胞的数量。
在机械应力组中，L3-4 水平的 LF 在 16 周和 52 周时表现出肥大，弹性纤维破坏和软骨基质产生。趋势检验表明，机械应力以时间依赖性方式诱导 LF 肥大、弹性纤维破坏和软骨基质产生，治疗前水平最低，52 周时最高。α-SMA 的免疫染色显示两组的血管数量相似，而机械应力组的肌成纤维细胞百分比在 16 周和 52 周时明显大于对照组。
我们证明了长期机械应力导致 LF 肥大，伴有进行性弹性纤维破坏和软骨基质产生，并伴有肌成纤维细胞增强。此外，报道的兔模型可以通过防止 LF 肥大来扩展，以阐明 LF 肥大的机制，并为 LSS 开发新的治疗策略。
SSSSSS。
