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.

ObjectiveTo study the effect of Guizhi Shaoyao Zhimutang （GSZMD） on cartilage destruction in mice with collagen-induced arthritis （CIA） and its mechanism. MethodThirty-six DBA/1 mice in SPF grades were randomly divided into 6 groups， namely， the normal group， the model group， the methotrexate （MTX） group， the low-dose GSZMD group， the medium-dose GSZMD group， and the high-dose GSZMD group. Except the normal group， mice in the other 5 groups were used to establish the model of CIA by secondary immunization. The mice were given normal saline， MTX （1.5 mg·kg^-1， 2 times a week）， and low， medium， and high-doses GSZMD （6.3， 12.6， 25.2 g·kg^-1·d^-1） by intragastric administration on the day of the onset of hind limb swelling for 4 weeks. The changes in the degree of foot swelling of mice in each group were observed and recorded. The content of matrix metalloproteinase （MMP）-1， MMP-3， MMP-9， and MMP-13 in serum was determined by enzyme-linked immunosorbent assay （ELISA）. The pathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining， and the cartilage destruction was observed by red fast green staining. The protein expression of the Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway in ankle joints were detected by Western blot. ResultAs compared with the normal group， the degree of foot swelling， the content of MMP-1， MMP-3， MMP-9， and MMP-13 in serum and the expression levels of phosphorylation （p）-JAK2/JAK2 and p-STAT3/STAT3 in ankle joints of the model group were increased （P<0.01）， and the joint damage was aggravated. As compared with the model group， the degrees of foot swelling of the mice in the MTX group and the low， medium， and high-dose GSZMD group were reduced （P<0.05， P<0.01）， and the content of MMP-1， MMP-3， MMP-9， and MMP-13 in serum was decreased （P<0.05， P<0.01）. The pathological joint damage was alleviated， and the expression levels of p-JAK2/JAK2 and p-STAT3/STAT3 in ankle joints were decreased in the MTX group and GSZMD groups （P<0.05， P<0.01）. ConclusionGSZMD can reduce the degree of joint swelling in mice with CIA， inhibit the expressions of MMP-1， MMP-3， MMP-9， and MMP-13， and alleviate the destruction of articular cartilage. Its mechanism is related to the JAK2/STAT3 signaling pathway.