Abstract：Objective: To investigate the effect of etomidate (ET) on cartilage damage in osteoarthritis (OA) rats and its regulation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. Methods: A total of 72 SPF SD male rats were randomly separated into 6 groups: sham operation group, model group, positive group (15mg/kg diclofenac sodium), and ET low (1.5mg/kg), medium (3mg/kg) and high-dose (6mg/kg) groups. The joint edema and weight-bearing asymmetry of the rats in each group were evaluated; the tenderness and thermal pain thresholds of rats in each group were detected; the pathological damage of cartilage in each group was observed by HE and Mankin score; the levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and cartilage oligomeric matrix protein (COMP) in rat serum were determined by enzyme-linked immunosorbent assay (ELISA); and the expression of matrix protease-13 (MMP-13) and pathway protein ERK and its phosphorylated p-ERK protein in cartilage tissue were determined by Western blot. Results: Compared with the sham-operation group, the right hind limb knee joint of the model group had edema and increased joint load-bearing asymmetry, cartilage tissue defects, and cartilage layer thinning, and the number of cartilage cells decreased, the levels of serum TNF-α, IL-1β, and COMP increased, the protein expression of MMP-13 and p-ERK1/2, and the ratio of p-ERK1/2/ERK1/2 in cartilage increased (P<0.05). Compared with the model group, the knee joint edema and joint load-bearing asymmetry of the right hind limb in the positive group and the different dose ET groups decreased, the cartilage damage was gradually repaired, the number of cells increased, the cells were evenly arranged, and the cartilage layer became thicker, the levels of serum TNF-α, IL-1β, and COMP decreased, the protein expression of MMP-13 and p-ERK1/2, and the ratio of p-ERK1/2/ERK1/2 in cartilage decreased (P<0.05). Conclusion: ET can alleviate the pathological damage of cartilage tissue in OA rats and reduce the expression of pro-inflammatory factors in serum, which may be achieved by inhibiting the activation of the MAPK/ERK signaling pathway.
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2023, Vol. 29 
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