骨关节炎(OA)发病率高，危害大，严重影响患者生活质量，晚期可致残。OA以软骨变性、破坏为特征，软骨细胞的肥大和凋亡是其主要病理基础，受软骨细胞生物钟基因异常表达调控。肾虚是OA的主要病机，课题组前期发现以骨碎补为君药的中药复方具有调节OA软骨细胞生物钟的作用。根据“软骨细胞生物钟”与中医“肾主骨”、“肾主生长发育”理论的一致性，我们提出：肾虚伴随着软骨细胞生物钟变化，骨碎补总黄酮通过调节软骨细胞生物钟PI3K/AKT/Bmal1通路调控OA软骨细胞凋亡。本项目拟以肾虚OA大鼠和SW1353细胞株为对象，观察肾虚OA大鼠PI3K/AKT/Bmal1通路的变化及骨碎补总黄酮对通路的影响，以细胞水平阻断实验验证该通路的特异性，从动物-细胞-分子体系逐层解析肾虚与OA软骨细胞生物钟的关系以及骨碎补总黄酮调控OA软骨细胞凋亡的作用机制，以期为补肾中药临床治疗OA提供实验基础。

With a high morbidity, osteoarthritis (OA) is the most common type of chronic arthritis that causes deformity and loss of function in advanced stage, which seriously influence patient's quality of life. OA is characterized by cartilage degeneration and damage. Cartilage cell hypertrophy and apoptosis, regulated by the abnormal genes expression of circadian clock in chondrocytes, is the main pathological basis of OA. Kidney deficiency is the main pathogenesis of OA. According to previous studies, we found that a traditional Chinese medicine (TCM) prescription with drynaria total flavonoids as core drug can regulates circadian clock in chondrocytes of OA. On the basis of the theoretical consistency among “circadian clock in chondrocytes”, “kidney governs bone” and “kidney governs growth, development and reproduction”, we hypothesize that: Kidney deficiency may be accompanied by the changes of circadian clock in chondrocytes, drynaria total flavonoids can regulate apoptosis of OA cartilage cell through the PI3K/AKT/Bmal1 signaling pathway. In this study, mice with OA and kidney deficiency and SW1353 cell line will be introduced as objects, animal and cell experiments will be conducted to explore changes of PI3K/AKT/Bmal1 in mice with OA and kidney deficiency, and effects of drynaria total flavonoids. A cell blocking experiment will also be conducted to further explore the special targets in PI3K/AKT/Bmal1 pathway. In a word, through the animal - cellular - molecular system, we will explore the relationship between kidney deficiency and circadian clock in chondrocytes of OA, as well as the effects of drynaria total flavonoids, in order to provide an experimental basis for the clinical application of tonifying kidney TCM in treating OA.