Study On The Therapeutic Effect And Mechanism Of Celastrol With Ankylosing Spondylitis Model PGIA Mice

Objective:Ankylosing spondylitis(AS)is a chronic,inflammatory,autoimmune disease.The typical site of onset is the sacroiliac joint and the attachment point of tendon ligament.Inflammation and pathological new bone formation are the two most important pathological features of AS.In the early stage,inflammation and bone erosion caused by inflammation are the main manifestations,while in the late stage,ectopic new bone formation can be caused,which can lead to spinal or peripheral joint fusion,leading to the loss of motor function and life ability of patients.Research on the mechanism shows that celastrol regulates various inflammatory mediators by inhibiting NF-κB,and inhibits pro-inflammatory cytokines(TNF,IL-2,IL-6,IL-8,IL-1β,IFN-γ And the production of pro-inflammatory enzymes to play an anti-inflammatory role,so it is inferred that celastrol may have a therapeutic effect on the inflammation and bone destruction of AS and become a potential therapeutic drug for AS.Animal models are very important for studying disease mechanisms and identifying new therapeutic drugs.The purpose of this study was to evaluate the therapeutic effects of celastrol on AS by using PGIA mice to mimic AS patients.Methods:PGIA mice models were constructed,and the treatment group was treated with celastrol.Comparisons and analyses were performed between the control group,PGIA mice and the treatment group mice by inflammation score,imaging performance,ELISA and Western Blot to determine whether the celastrol could show therapeutic effects on PGIA mice and to explore the therapeutic mechanism of celastrol.Results:PGIA mice showed symptoms similar to AS,and the inflammatory and imaging manifestations of mice treated with triptolide were relieved,and TNF-α,IL-1β,the content of IL-6 decreased,and the expression of NF-κB and RUNX2 in the ligaments and soft tissues at the attachment point was down regulated,and the expression of caspase3 and other apoptosis-related genes was up regulated.Conclusion:Celastrol can reduce the inflammatory reaction,bone erosion,destruction and ossification of the body by reducing the content of inflammatory factors,down-regulating the expression of inflammatory pathways such as NF-κB,and up-regulating the apoptosis of fibroblasts,thus playing a therapeutic role in PGIA mice,and has the potential to become an effective therapeutic drug for AS in the future.