The expression of P16 and S100 associated with elastin degradation and fibrosis of the Ligamentum Flavum hypertrophy

The expression of P16 and S100 associated with elastin degradation and fibrosis of the Ligamentum Flavum hypertrophy
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DOI:
10.1186/s12891-019-2825-4
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发表时间:
2019-10-22
影响因子:
2.3
通讯作者:
Zhu, Rusen
Zhu, Rusen
中科院分区:
医学3区
文献类型:
--
作者:
Hu, Wei;Kan, Shunli;Zhu, Rusen

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腰椎管狭窄症(LSS)的特征之一是黄韧带(LF)的弹性蛋白降解和纤维化。然而,导致这些组织学变化的生化因素尚不清楚。P16和S100参与了创伤愈合和纤维化疾病中瘢痕的形成和胶原的形成。本研究探讨P16和S100蛋白的表达与腰椎管肥厚性腰椎管纤维化的关系。方法30例单节段腰椎管综合征(SLSS)、30例双节段腰椎管狭窄症(DLSS)和30例L4/5腰椎间盘突出症(LDH)患者手术切除腰椎管标本。用轴位T1加权MRI测量LF厚度。根据苏木精-伊红(HE)和Verhoff‘s Van Gieson’s(VVG)染色对LF弹性蛋白降解程度和纤维化程度进行分级。结果DLSS组LF的绝对厚度和相对厚度均大于SLSS组和LDH组(p<0.05)。SLSS组和DLSS组从背侧到硬脑膜侧的弹性组织明显增多。DLSS组胶原沉积和弹性组织的数量明显高于SLSS组和LDH组(p&lt;0.05)。DLSS组标本均有P16阳性表达,尤以背层阳性表达最多。SLSS组几乎所有样本P16部分阳性。LDH组硬膜层和背层P16染色均为阴性。3组大鼠的LF背侧层均有S100染色。结论DLSS患者LF的弹力蛋白降解和纤维化程度较SLSS和LDH患者严重。P16的表达与LSS患者的LF纤维化及增厚有关,提示P16的表达可能与LSS患者的LF肥大有关。LF肥大过程可能与S100的高表达无关。
BackgroundOne of the characteristics of lumbar spinal stenosis (LSS) is elastin degradation and fibrosis in the ligamentum flavum (LF). However, the biochemical factors that cause these histologic changes is unclear. P16 and S100 participate in scar formation and collagen development in wound healing and fibrosis diseases. In this study, we investigate the association between P16 and S100 expression and the fibrosis of the hypertrophic LF in LSS.MethodsThe LF specimens were surgically obtained from 30 patients with single-segment LSS (SLSS), 30 patients with double-segment LSS (DLSS) and 30 patients with L4/5 lumbar disc herniation (LDH). The LF thickness was measured by axial T1-weighted MRI. The extent of LF elastin degradation and fibrosis were graded based on hematoxylin-eosin (HE) and Verhoff's Van Gieson's (VVG) stain, respectively. The localization of P16 and S100 was determined by immunohistochemistry.ResultsThe Absolute and relative LF thickness were greater in the DLSS group compared with the SLSS and LDH groups (p< 0.05). The elastic tissue from the dorsal aspect to the dural aspect in SLSS and DLSS groups was significantly increased. The amount of collagen deposition and elastic tissue is significantly higher in the DLSS group compared with the SLSS and LDH groups (p< 0.05). The specimens in the DLSS group showed positive staining of P16, especially in the dorsal layer. Almost all samples in the SLSS group were partially positive for P16. The LDH group showed negative staining of P16 in both the dural and dorsal layers. All the three groups were stained with S100 in the dorsal layer of the LF. On the contrary, S100 staining was absent in the dural layer of the LF in the three groups.ConclusionsElastin degradation and fibrosis of the LF in the DLSS patients is more severe compared with the SLSS and LDH patients. Increased expression of P16 associated with LF fibrosis and thickness, suggested that the expression of P16 may related to LF hypertrophy in the patients who suffer with LSS. LF hypertrophy process may not be associated with high expression of S100.