中文摘要：

目的 建立大鼠激素性股骨头坏死模型并研究Toll样受体4（TLR4）信号通路在激素性股骨头坏死中的作用机制.方法 成年雄性SD大鼠随机分为模型组、干预组,每组各24只,按照甲强龙20 mg/kg的剂量给予双侧臀大肌交替肌注造模,1周1次,共8周.其中干预组在每次激素注射后,同时给予10 mg/kg TAK242药物静脉注射;另12只大鼠设为对照组,仅在同等条件下给予生理盐水肌注.在激素注射后的8、10、12周时分别以过量麻醉法处死各组动物,采用ELISA测定血清中抗酒石酸酸性磷酸酶（TRAP）的含量,并对股骨头进行组织病理学观察和TRAP特异性染色观察.分别提取各组大鼠股骨头总mRNA和总蛋白,采用RT PCR和Western blot技术检测TLR4、髓样细胞分化因子88（MyD88）、NF-κB p65和单核细胞趋化蛋白（MCP-1）的mRNA及蛋白的表达.结果 模型组股骨头坏死的组织病理学表现明显,其中血清TRAP含量、TRAP特异性染色面积、各因子的mRNA和蛋白含量表达均较其他两组有统计学差异（P＜0.05）.干预组与空白对照组的各指标检测结果差异均无统计学意义（P＞0.05）.结论 大剂量激素的使用可以引起TLR4信号通路过度激活从而介导激素性股骨头坏死的发生.

英文摘要：

Objective To establish a rat model to investigate Toll-like receptor 4 （TLR4） signaling pathway associated with the pathogenesis of steroid-induced femoral head osteonecrosis.Methods Adult male SD rats were randomly divided into model group and intervention group with 24 rats in each,and then were injected intramuscularly with 20 mg/kg methylprednisolone （MP） via bilateral gluteus maximus alternatively once a week for 8 weeks.The rats in intervention group were injected intravenously with 10 mg/kg TAK242 before each MP administration.A control group consisting of 12 rats received saline injection.All animals were sacrificed at week 8,10 or 12 from the first MP injection,respectively.The analyses of histopathology and TRAP staining were performed and the concentration of tartrate-resistant acid phosphatase （TRAP） in serum was tested.The mRNA and protein expressions of TLR4,MyD88,NF-κB p65 and MCP-1 were detected by quantitative real-time PCR and Western blot.Results Femoral head osteonecrosis was observed in the model rats,and the concentration and positive staining of TRAP,the mRNA and protein expression levels of all the factors were enhanced significantly in model group compared with that in intervention group and control group （P ＜ 0.05）.There was no significant difference in the tested factors between intervention group and control group （P＞0.05）.Conclusion Excessive dosage of corticosteroids can induce femoral head osteonecrosis via the abnormal activation of TLR4 signaling pathway.