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甘油诱导的脊柱旁肌退变导致野生型小鼠出现严重的脊柱后凸畸形。

Glycerol induced paraspinal muscle degeneration leads to hyper-kyphotic spinal deformity in wild-type mice.

机构信息

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.

Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Bone and Joint Institute, University of Western Ontario, London, ON, Canada.

出版信息

Sci Rep. 2023 May 20;13(1):8170. doi: 10.1038/s41598-023-35506-9.

Abstract

Degenerative spinal disorders, including kyphotic deformity, are associated with a range of degenerative characteristics of the paraspinal musculature. It has therefore been hypothesized that paraspinal muscular dysfunction is a causative factor for degenerative spinal deformity; however, experimental studies demonstrating causative relationships are lacking. Male and female mice received either glycerol or saline injections bilaterally along the length of the paraspinal muscles at four timepoints, each separated by 2 weeks. Immediately after sacrifice, micro-CT was performed to measure spinal deformity; paraspinal muscle biopsies were taken to measure active, passive and structural properties; and lumbar spines were fixed for analysis of intervertebral disc (IVD) degeneration. Glycerol-injected mice demonstrated clear signs of paraspinal muscle degeneration and dysfunction: significantly (p < 0.01) greater collagen content, lower density, lower absolute active force, greater passive stiffness compared to saline-injected mice. Further, glycerol-injected mice exhibited spinal deformity: significantly (p < 0.01) greater kyphotic angle than saline-injected mice. Glycerol-injected mice also demonstrated a significantly (p < 0.01) greater IVD degenerative score (although mild) at the upper-most lumbar level compared to saline-injected mice. These findings provide direct evidence that combined morphological (fibrosis) and functional (actively weaker and passively stiffer) alterations to the paraspinal muscles can lead to negative changes and deformity within the thoracolumbar spine.

摘要

退行性脊柱疾病,包括后凸畸形,与多种脊柱旁肌肉的退行性特征有关。因此,有人假设脊柱旁肌肉功能障碍是退行性脊柱畸形的一个致病因素;然而,缺乏证明因果关系的实验研究。雄性和雌性小鼠在四个时间点分别接受双侧脊柱旁肌肉的甘油或盐水注射,每个时间点间隔 2 周。在处死立即进行 micro-CT 以测量脊柱畸形;取脊柱旁肌肉活检以测量主动、被动和结构特性;并固定腰椎以分析椎间盘(IVD)退变。甘油注射的小鼠表现出明显的脊柱旁肌肉退化和功能障碍迹象:与盐水注射的小鼠相比,胶原含量显著增加(p<0.01),密度降低,绝对主动力降低,被动刚度增加。此外,甘油注射的小鼠还表现出脊柱畸形:与盐水注射的小鼠相比,后凸角度显著增加(p<0.01)。甘油注射的小鼠在上最腰椎水平的椎间盘退行性评分也显著增加(尽管较轻)(p<0.01)与盐水注射的小鼠相比。这些发现提供了直接证据,表明脊柱旁肌肉的形态(纤维化)和功能(主动较弱和被动较硬)改变的综合作用可导致胸腰椎的负面变化和畸形。

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