Department of Musculoskeletal Biomechanics and Surgical Development, School of Medicine, Sapporo Medical University, Sapporo, Japan; Department of Legal Medicine and Molecular Alcohology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
Int J Exp Pathol. 2013 Oct;94(5):312-9. doi: 10.1111/iep.12035.
Alcohol-induced osteonecrosis of the femoral head (ONFH) is observed in alcohol abusers and patients with alcoholic fatty liver disease. It has been reported that Toll-like receptor 4 (TLR4) signalling plays a crucial role in the pathogenesis of alcoholic fatty liver disease. We previously reported a corticosteroid-induced ONFH rat model, and suggested that TLR4 signalling contributes to the pathogenesis of ONFH. Thus, it is thought that the pathogenesis of alcohol-induced ONFH is probably similar to that of corticosteroid-induced ONFH. The aim of this study was to develop a new animal model for alcohol-induced ONFH and to evaluate the relationship between the pro-inflammatory response via TLRs and the development of ONFH in rats. Male Wistar rats were fed a Lieber-DeCarli liquid diet containing 5% ethanol (experimental group) or dextran (control group) for 1-24 weeks. Histopathological and biochemical analyses were performed. Feeding the ethanol-containing liquid diet resulted in the development of ONFH with hepatic steatosis, hepatic dysfunction and hyperlipidaemia, whereas feeding the dextran-containing diet did not cause ONFH. However, we could not recognize any relationship between the pro-inflammatory response via TLR4 and the development of alcohol-induced ONFH. Thus in this study we have developed a new rat model for alcohol-induced ONFH based on the feeding of an ethanol liquid diet. ONFH was observed within seven days from the start of feeding with 5% ethanol-containing liquid diet. Although this was linked to hepatic steatosis, a TLR4 association was not a feature of this model.
酒精性股骨头坏死（ONFH）可见于酗酒者和酒精性脂肪肝患者。有报道称，Toll 样受体 4（TLR4）信号在酒精性脂肪肝的发病机制中起关键作用。我们之前报道了一种皮质类固醇诱导的 ONFH 大鼠模型，并提出 TLR4 信号参与了 ONFH 的发病机制。因此，人们认为酒精性 ONFH 的发病机制可能与皮质类固醇诱导的 ONFH 相似。本研究旨在建立一种新的酒精诱导的 ONFH 动物模型，并评估 TLR 介导的促炎反应与大鼠 ONFH 发展之间的关系。雄性 Wistar 大鼠给予含有 5%乙醇（实验组）或葡聚糖（对照组）的 Lieber-DeCarli 液体饮食 1-24 周。进行组织病理学和生化分析。用含乙醇的液体饮食喂养会导致 ONFH 合并肝脂肪变性、肝功能障碍和高脂血症，而用含葡聚糖的饮食喂养不会导致 ONFH。然而，我们无法识别 TLR4 介导的促炎反应与酒精诱导的 ONFH 发展之间的任何关系。因此，在这项研究中，我们基于喂食含乙醇的液体饮食，建立了一种新的酒精诱导的 ONFH 大鼠模型。从开始喂食含 5%乙醇的液体饮食七天后就观察到了 ONFH。尽管这与肝脂肪变性有关，但该模型的 TLR4 相关性不是其特征。
