HIF-1α在缓解关节软骨细胞内质网应激胁迫中重塑肉鸡股骨头坏死软骨稳态的机理研究

股骨头坏死（femoral head necrosis，FHN）是肉鸡养殖最常见的腿病之一，不仅导致经济损失，而且危害动物福利。我们前期工作发现关节软骨细胞内质网应激促进FHN肉鸡软骨稳态失衡，关节软骨损伤。低氧诱导因子-1α（HIF-1α）可缓解关节软骨细胞内质网应激，抑制其凋亡，影响肉鸡FHN进程，但机制尚不明确。本研究在建立肉鸡FHN模型及HIF-1α基因过表达及沉默关节软骨细胞模型的基础上，通过骨质、骨代谢标志物检测，组织病理学观察，组学和生物信息学技术分析，研究HIF-1α表达与肉鸡FHN关节软骨损伤关联性，HIF-1α对关节软骨细胞功能基因表达的影响，缓解软骨细胞内质网应激、调控软骨稳态的信号传导途径和反馈作用机制。系统阐明HIF-1α重塑肉鸡FHN软骨稳态，修复软骨损伤的作用和临床意义，为肉鸡FHN发病机理和防控研究提供依据，为比较医学提供借鉴。

Femoral head necrosis (FHN) is one of the most common leg diseases in broilers, which not only leads economic losses, but also harms poultry welfare. Our previous works showed that endoplasmic reticulum stress of articular chondrocytes promoted the imbalance of cartilage homeostasis and articular cartilage destruction in FHN-affected broilers. Hypoxia inducible factor-1α (HIF-1α) can alleviate endoplasmic reticulum stress of articular chondrocytes, inhibit chondrocyte apoptosis, and affect the pathogenesis of FHN in broilers, but the mechanisms are still unclear. In the present study, based on the establishment of FHN model in broilers, HIF-1α gene overexpression and silencing of articular chondrocytes model, it is designed to study the relationship between HIF-1α expression and cartilage destruction in FHN-affected broilers,the effects of HIF-1α on the functional gene expression of articular chondrocytes, the signaling pathways and feedback mechanisms of alleviating chondrocyte endoplasmic reticulum stress and regulating cartilage homeostasis by the detection of bone quality and metabolic markers, histopathological obseravation, omics and bioinformatics analyses.The purpose of the present study is to systematically clarify the roles and clinical significance of HIF-1α in remodeling cartilage homeostasis and repairing cartilage destruction, to provide the evidence for the pathogenesis, control and treatment of FHN in broilers, and to provide references for comparative medicine.