Okazaki S, Nishitani Y, Nagoya S, Kaya M, Yamashita T, Matsumoto H
Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Rheumatology (Oxford). 2009 Mar;48(3):227-32. doi: 10.1093/rheumatology/ken462. Epub 2009 Jan 7.
Osteonecrosis of the femoral head is observed in patients treated with steroids. However, the pathogenesis of femoral head osteonecrosis remains unclear. We established a rat model with femoral head osteonecrosis by injecting lipopolysaccharide (LPS) and steroid, and assessed the consequences of this on femoral head histology, the systemic immune response and lipid synthesis.
Male Wistar rats were injected intravenously on days 0 and 1 with 2 mg/kg LPS and intramuscularly with 20 mg/kg methylprednisolone on days 3, 4 and 5. The animals were sacrificed 1, 2, 3 or 4 weeks after the last methylprednisolone injection. Histopathological and biochemical analyses were performed every week.
Osteonecrosis of the femoral head was observed in the rats. The plasma triglyceride concentrations had decreased significantly by weeks 2 and 3. The total plasma cholesterol concentrations had increased significantly by week 1 but then decreased significantly by week 4. The plasma concentrations of IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma and TNF-alpha had increased significantly by week 1. These cytokines can all be induced by toll-like receptor 4 (TLR4) signalling.
LPS and methylprednisolone induced osteonecrosis of the femoral head in rats and this was associated with a disruption of the innate immune system and lipid synthesis. These findings suggest that the TLR4 signalling pathway plays an important role in the pathogenesis of femoral head osteonecrosis.
在接受类固醇治疗的患者中观察到股骨头坏死。然而，股骨头坏死的发病机制仍不清楚。我们通过注射脂多糖（LPS）和类固醇建立了股骨头坏死大鼠模型，并评估了其对股骨头组织学、全身免疫反应和脂质合成的影响。
雄性Wistar大鼠在第0天和第1天静脉注射2mg/kg LPS，并在第3、4和5天肌肉注射20mg/kg甲泼尼龙。在最后一次注射甲泼尼龙后1、2、3或4周处死动物。每周进行组织病理学和生化分析。
在大鼠中观察到股骨头坏死。血浆甘油三酯浓度在第2周和第3周显著降低。血浆总胆固醇浓度在第1周显著升高，但在第4周显著降低。血浆中IL-1β、IL-2、IL-4、IL-6、IL-10、GM-CSF、IFN-γ和TNF-α的浓度在第1周显著升高。这些细胞因子均可由Toll样受体4（TLR4）信号通路诱导产生。
LPS和甲泼尼龙诱导大鼠股骨头坏死，这与天然免疫系统和脂质合成的破坏有关。这些发现表明，TLR4信号通路在股骨头坏死的发病机制中起重要作用。
