James Gregory, Sluka Kathleen A, Blomster Linda, Hall Leanne, Schmid Annina B, Shu Cindy C, Little Christopher B, Melrose James, Hodges Paul W
Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, QLD, 4072, Australia.
Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, IA, USA.
Eur Spine J. 2018 Aug;27(8):1744-1756. doi: 10.1007/s00586-018-5652-7. Epub 2018 Jun 12.
Intervertebral disk (IVD) lesion and its subsequent degeneration have a profound effect on the multifidus muscle. The subacute/early chronic phase of multifidus remodeling after IVD lesion has been proposed to be regulated by inflammatory processes. The balance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages plays an important role in maintaining tissue integrity after injury. The localization, polarization of macrophage subtypes and their mediation of the pro-inflammatory cytokine tumor necrosis factor (TNF) are unknown in paraspinal muscles during IVD degeneration. A sheep model of IVD degeneration was used to investigate the role of macrophages and TNF in the structural alterations that occur within the multifidus muscle.
Anterolateral lesions were induced at L3-4 IVD in sheep. Multifidus muscle tissue at L4 was harvested 3 and 6 months after lesion and used for immunofluorescence assays to examine total macrophage number, macrophage polarization between M1 and M2, and to assess the localization of TNF expression in muscle, adipose and connective tissues from injured and naïve control animals.
A greater proportion of M1 macrophages is present in muscle at both 3 and 6 months after IVD lesion, and adipose tissue at 6 months. Total number of macrophages is unchanged. At 6 months, expression of TNF is increased in adipose and connective tissue and the proportion of TNF expressed by M1 macrophages is increased.
These data support the proposal that macrophages and TNF (pro-inflammatory cytokine) play an active role in the subacute/early chronic phase of remodeling in muscle, adipose and connective tissues of the multifidus during IVD degeneration. This presents a novel target for treatment. These slides can be retrieved under Electronic Supplementary Material.
椎间盘（IVD）损伤及其后续退变对多裂肌有深远影响。有研究提出，IVD损伤后多裂肌重塑的亚急性/早期慢性阶段受炎症过程调控。促炎（M1）巨噬细胞和抗炎（M2）巨噬细胞之间的平衡在损伤后维持组织完整性方面起重要作用。在IVD退变过程中，椎旁肌内巨噬细胞亚型的定位、极化及其对促炎细胞因子肿瘤坏死因子（TNF）的介导作用尚不清楚。本研究采用绵羊IVD退变模型，探讨巨噬细胞和TNF在多裂肌结构改变中的作用。
在绵羊L3-4椎间盘处诱导前外侧损伤。损伤后3个月和6个月采集L4水平的多裂肌组织，用于免疫荧光检测，以检查总巨噬细胞数量、M1和M2巨噬细胞之间的极化情况，并评估TNF在受伤和未受伤对照动物的肌肉、脂肪和结缔组织中的表达定位。
IVD损伤后3个月和6个月，肌肉中M1巨噬细胞比例均较高，6个月时脂肪组织中M1巨噬细胞比例也较高。巨噬细胞总数不变。6个月时，脂肪和结缔组织中TNF表达增加，且M1巨噬细胞表达的TNF比例增加。
这些数据支持以下观点，即巨噬细胞和TNF（促炎细胞因子）在IVD退变期间多裂肌的肌肉、脂肪和结缔组织重塑的亚急性/早期慢性阶段发挥积极作用。这为治疗提供了一个新的靶点。这些幻灯片可在电子补充材料中获取。
