Bunn Jonathan R, Canning John, Burke George, Mushipe Moses, Marsh David R, Li Gang
Trauma Research Group, Department of Trauma and Orthopaedic Surgery, Queen's University Belfast, Musgrave Park Hospital, Stockman's Lane, BT9 7JB, Northern Ireland, UK.
J Orthop Res. 2004 Nov;22(6):1336-44. doi: 10.1016/j.orthres.2004.03.013.
Poor healing of high-energy fractures is often associated with severe muscle damage. This may be partly due to the production, by the injured muscle, of inflammatory cytokines that somehow misdirect bone healing. In order to investigate this question, an animal model was established which embodies a controlled degree of muscle injury with a dose response to the energy absorbed, that can be characterised histologically. Using a custom crush jig, 60 CFLP mice had either 100 or 200 g masses dropped from a fixed height onto the quadriceps muscle, with mechanical measurement of the impact. Energy of impact was reliably and significantly different between the small and large impact conditions, though there was more variability when the large mass was used. Animals were sacrificed at day 2, 4, 8, 16, and 24 post-injury. Muscle histomorphometry at all time points and immunohistochemistry for IL-1beta, IL-6, and TNF-alpha up to day 8 were used as measures of muscle damage, inflammation and repair. Histological sections were analysed into areas of normal muscle fibres, damaged/regenerating muscle fibres and fibrous/inflammatory infiltrate. Early histological response was similar between the two groups; the large crush group displayed significantly greater areas of inflammatory infiltrate and damaged muscle at the later time points after day 8. In the large crush group, IL-1beta and IL-6 expression were significantly higher at day 2 and TNF-alpha was higher at day 8 when compared to the small crush group. The experiment demonstrated that more severe injury to muscle was reliably followed by increased inflammatory cytokine production and a greater degree of inflammation and fibrosis. Increased production of inflammatory cytokines such as TNF-alpha and IL-1beta in the damaged muscles may activate macrophages and recruit fibroblasts, promote scar formation and lead to delayed union or non-union of the adjacent fracture(s).
高能骨折愈合不良通常与严重的肌肉损伤有关。这可能部分归因于受伤肌肉产生的炎性细胞因子，这些因子以某种方式误导了骨愈合。为了研究这个问题，建立了一种动物模型，该模型体现了可控程度的肌肉损伤，对吸收的能量有剂量反应，并且可以通过组织学进行表征。使用定制的挤压夹具，将60只CFLP小鼠的股四头肌分别受到从固定高度落下的100克或200克重物撞击，并对撞击进行力学测量。尽管使用大质量重物时变异性更大，但小撞击和大撞击条件下的撞击能量可靠且显著不同。在损伤后第2、4、8、16和24天处死动物。在所有时间点进行肌肉组织形态计量学分析，并在第8天之前对IL-1β、IL-6和TNF-α进行免疫组织化学分析，以作为肌肉损伤、炎症和修复的指标。组织学切片被分析为正常肌纤维、受损/再生肌纤维和纤维/炎性浸润区域。两组早期组织学反应相似；大挤压组在第8天后的后期时间点显示出明显更大的炎性浸润和受损肌肉区域。与小挤压组相比，大挤压组在第2天IL-1β和IL-6表达显著更高，在第8天TNF-α更高。该实验表明，更严重的肌肉损伤确实会导致炎性细胞因子产生增加以及更大程度的炎症和纤维化。受损肌肉中TNF-α和IL-1β等炎性细胞因子产生增加可能会激活巨噬细胞并募集成纤维细胞，促进瘢痕形成，并导致相邻骨折延迟愈合或不愈合。
