以“血瘀”理论指导治疗:解读膝骨关节炎“铁超载”的相关机制

An insight into the mechanism of iron overload in knee osteoarthritis under the theory of blood stasis

背景:膝骨关节炎多发于中老年人,是一类严重影响患者的生活质量甚至有致残风险的疾病。因此,膝骨关节炎的发病机制以及治疗手段已成为研究的焦点。在祖国医学中,膝骨关节炎常以“痹”论治,并与中医“血瘀”理论中血行瘀滞、血脉阻络而致之“痹”紧密相关。铁超载是一类因铁代谢紊乱导致的病理状态,其与中医“血瘀”理论的发病特点、临床表现等高度重合,是促进膝骨关节炎发展的危险因素。目的:基于“血瘀”理论,就铁超载对软骨代谢以及软骨下骨重建的影响展开综述,为中医药治疗膝骨关节炎奠定了全新理论基础,也为探究活血中药干预骨组织后期治疗作用的相关机制提供理论依据。方法:通过检索中国知网、万方数据、PubMed及Web of Science数据库获得文献,中文检索词为“铁死亡,铁,铁超载,骨关节炎,血瘀”以及英文检索词为“ferroptosis,iron,iron overload,osteoarthritis,TCM”,最终纳入文献76篇进行综述分析。结果与结论:①文章针对“血瘀”理论治疗膝骨关节炎的潜力进行发掘,发现“血瘀”是膝骨关节炎进展中至关重要的部分,表明“血瘀”理论是中医治疗膝骨关节炎的关键所在。②“血瘀”与铁超载在致病因素、临床表现、发病特点上有高度的相似性,提示了“血瘀”理论治疗铁超载的可能性,说明铁超载可能是“血瘀”理论治疗膝骨关节炎的重要机制基础,活血类药物的提取物有着缓解铁超载并治疗膝骨关节炎的作用,但具体机制尚不明确。③“血瘀”理论与铁超载的关系及相关机制是未来膝骨关节炎的重要研究方向,可为中医临床开发新药、创新用法等中医现代化手段提供了理论基础,对临床有一定的指导意义。

BACKGROUND:Knee osteoarthritis is a common disease in middle-aged and elderly people.It is a kind of disease that seriously affects the quality of life of patients and even has the risk of disability.Therefore,the pathogenesis and treatment of knee osteoarthritis have become the focus of research.In Chinese medicine,knee osteoarthritis is often treated as“biness,”which is closely related to“biness”caused by blood stasis and blood vessels blocking collaterals in the theory of“blood stasis”in traditional Chinese medicine.Iron overload is a kind of pathological state caused by iron metabolism disorder,which highly coincides with the pathogenic characteristics and clinical manifestations of the“blood stasis”theory of traditional Chinese medicine,and is a risk factor that promotes the development of knee osteoarthritis.OBJECTIVE:Based on the“blood stasis”theory,to summarize the effects of iron overload on cartilage metabolism and subchondral bone reconstruction,to lay a new theoretical foundation for the treatment of knee osteoarthritis with traditional Chinese medicine,and to explore the therapeutic effect of traditional Chinese medicine for promoting blood circulation after interfering with bone tissue.METHODS:CNKI,WanFang database,PubMed and Web of Science databases were searched for relevant literature.The Chinese search terms were“ferroptosis,iron,iron overload,osteoarthritis,blood stasis”and the English search terms were“ferroptosis,iron,iron overload,osteoarthritis,TCM.”In the end,76 articles were included for further review.RESULTS AND CONCLUSION:First of all,we explored the potential of the“blood stasis”theory in treating knee osteoarthritis,and found that“blood stasis”is a crucial part in the progress of knee osteoarthritis,indicating that the“blood stasis”theory is the key to the treatment of knee osteoarthritis in traditional Chinese medicine.Secondly,“blood stasis”and iron overload have a high degree of similarity in pathogenic factors,clinical manifestations,and pathogenic characteristics,suggesting the possibility of“blood stasis”theory in treating iron overload.This finding reminds us that iron overload may be an important mechanistic basis for the“blood stasis”theory in the treatment of knee osteoarthritis.The extracts of blood-activating drugs can relieve iron overload and treat knee osteoarthritis,but the specific mechanism is still unclear.Therefore,we believe that the relationship between“blood stasis”theory and iron overload and related mechanisms are important research directions for knee osteoarthritis in the future.The related mechanism of“blood stasis”theory to alleviate iron overload and then treat knee osteoarthritis also provides a theoretical basis for the modernization of traditional Chinese medicine,such as the development of new drugs and innovative usage,and has certain guiding significance for clinical practice.