Establishing an intervertebral disc degeneration model in bipedal rats via a modified feeding approach

通过改良的喂养方法建立双足大鼠椎间盘退变模型

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Abstract

Mechanical stress is an important factor that induces intervertebral disc degeneration (IVDD). However, the established in vivo models are inadequate for simulating the natural progression of disc degradation induced by mechanical forces in daily life. This study aimed to explore an improved feeding approach to compensate for the inherent deficiencies of the traditional bipedal rat IVDD model. Bipedal rats in the experimental group (M group) were placed into cages specifically designed to induce them to walk upright following constantly sliding food to increase the intradiscal pressure on their lumbar spine. Traditional bipedal rats (T group) and intact homochromous rats (C group) were fed simultaneously. We then analyzed the outcome using general indicators (weight gain, ΔW), bipedal behavior (upright posture time) assessment, magnetic resonance imaging (MRI), and determination of disc histological grades from morphological observations and histological analyses (H&E and safranin O staining and immunohistochemical staining). Rats in the M group adapted to the upright posture more quickly and maintained their spines standing longer than those in the T group did (P < 0.05). The discs of rats in the M group exhibited a progressive decline in both the MRI index and signal intensity at 3 months, which was aggravated through 6 months (P < 0.05). Histological analyses with H&E and safranin O green staining of the discs of rats at 6 months revealed that IVDD in the M group was more severe than that in the C and T groups (P < 0.05). The upregulated expression of collagen I and typical inflammatory cytokines (COX-2, iNOS and TNF-α) was detected in the IVD tissues of the rats in the M group (P < 0.05). The present study provides a novel and appropriate approach for establishing a cumulative mechanical stress-triggered IVDD model.

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