中药干预软骨细胞自噬防治膝骨关节炎研究进展

Research progress on Traditional Chinese Medicine interventionin autophagy for prevention and treatment of knee osteoarthritis

关键词:  膝骨关节炎  软骨细胞  自噬  中药

Key words:  Knee osteoarthritis  Chondrocyte  Autophagy  Traditional Chinese Medicine

摘要:

膝关节是骨关节炎最为好发的关节,也是导致患者功能活动受损的重要因素。膝骨关节炎(knee osteoarthritis, KOA)是一种以膝关节疼痛为主要临床表现的退行性疾患。从宏观层面讲,KOA的发病与衰老、创伤、膝关节脱位和肥胖等因素引起的关节生物力学变化有关。从微观角度讲,KOA是由代谢综合征、骨代谢异常、细胞因子和相关酶、基因突变以及血浆脂联素的改变所引起。随着研究的不断深入,发现软骨细胞自噬是KOA重要的病理机制,自噬通过溶酶体的作用降解受损蛋白及损伤衰老的细胞器,是维持细胞稳态的重要机制。本文对中医药干预软骨细胞自噬防治KOA的具体分子机制进行了归纳总结,发现其具有双向调控,主要体现在促进细胞自噬、抑制细胞自噬两个方面。一方面,中医药可通过发挥对细胞自噬的促进作用,加速对炎性因子的清除,下调促炎细胞因子的释放,降低其炎症反应；另一方面,中医药通过发挥对细胞自噬的抑制作用,减轻软骨细胞的炎症。因此,本文就中医药调控软骨细胞自噬防治KOA领域的突破与进展进行综述,阐述软骨细胞自噬与KOA发生、发展的关系,并系统总结中药单体、中药提取物及中药复方干预细胞自噬治疗膝骨关节炎的最新研究成果,以期完善KOA的发病机制,为药物治疗的深入研究提供新思路,为临床用药提供理论依据。

Abstract:

The knee joint is the joint most commonly involved in osteoarthritis (OA) and is an important factor in patient morbidity and impaired function. Knee osteoarthritis (KOA) is a degenerative disease in which knee pain is the main clinical manifestation. From a macroscopic perspective, KOA is mainly related to joint biomechanical changes caused by aging, trauma, knee dislocation, and obesity. At the microscopic level, it is caused by metabolic syndrome, abnormal bone metabolism, cytokines and related enzymes, gene mutations, and changes in plasma adiponectin. Previous studies have found that the pathogenesis of KOA is related to autophagy, which degrades damaged proteins, damages senile organelles through lysosomes, and is an important mechanism for maintaining cell homeostasis. In this paper, we summarize the specific molecular mechanism of traditional Chinese medicine (TCM) intervention in the prevention and treatment of KOA caused by autophagy. We found that the primary function of TCM in KOA was the promotion and inhibition of cell autophagy. Importantly, by promoting autophagy, TCM can accelerate clearance of inflammatory factors, downregulate the release of pro-inflammatory cytokines, and reduce the inflammatory response, in addition to reducing the inflammation of chondrocytes by inhibiting autophagy. Based on our review of the latest research progress globally, here we briefly explain the relationship between autophagy and the occurrence and development of KOA and summarize the latest reports on intervention into KOA using TCM monomers, extracts, and compounds. Our findings provide new directions for in-depth study of the pathogenesis and drug treatment of KOA and, ultimately, a better theoretical basis for clinical treatment.