淫羊藿苷调控HMGB1/RAGE通路对强直性脊柱炎大鼠破骨细胞分化的影响OA

Objective:To investigate the effect of icariin(ICA)on osteoclast differentiation in rats with ankylosing spondy-litis(AS)via modulation of the HMGB1/RAGE pathway.Methods:The AS rat models were constructed by intraperitone-al injection of bovine proteoglycan combined with adjuvant in several doses and were randomly assigned into the Model group,the positive drug-sulfasalazine(Positive)group,the low-and high-dose icariin(ICA-L,ICA-H)groups,and the high-dose icariin+HMGB1 activator(ICA-H+rHMGB1)group.Another 8 rats were taken as the Control group.ELISA experiments were conducted to detect the levels of serum inflammatory cytokines(IL-6,IL-17,TNF-α)and osteoclast functional markers(TRAP,CTSK,MMP9).Detection of pathological changes in sacroiliac joint tissue by HE staining.TRAP staining was used to detect the number of osteoclasts.The positive expression of NFATc1 in the sacro-iliac joint tissue was detected by immunohistochemistry.The expression of proteins related to the HMGB1/RAGE path-way was detected by Western blotting.Results:Compared with the Control group,the sacroiliac joint tissues of rats in the Model group showed synovial hyperplasia,inflammatory cell infiltration and cartilage damage;meanwhile,the serum levels of IL-6,IL-17,TNF-α,TRAP,CTSK and MMP9,the number of osteoclasts in sacroiliac joint tissues,the positive expres-sion of NFATc1,as well as the protein expression levels of HMGB1,RAGE and p-NF-κB p65/NF-κB p65 were signifi-cantly increased(P＜0.05).Compared with the Model group,the pathological damage of sacroiliac joint tissues was alle-viated in rats of the low-dose ICA group,high-dose ICA group and Positive group;meanwhile,the serum levels of IL-6,IL-17,TNF-α,TRAP,CTSK and MMP9,the number of osteoclasts in sacroiliac joint tissues,the positive expression of NFATc1,as well as the protein expression levels of HMGB1,RAGE and p-NF-κB p65/NF-κB p65 were significantly decreased(P＜0.05).Compared with the ICA-H group,rats in the ICA-H+rHMGB1 group showed increased inflam-matory cell infiltration and aggravated pathological damage in sacroiliac joint tissues;meanwhile,the serum levels of IL-6,IL-17,TNF-α,TRAP,CTSK and MMP9,the number of osteoclasts in sacroiliac joint tissues,the positive expression of NFATc1,as well as the protein expression levels of HMGB1,RAGE and p-NF-κB p65/NF-κB p65 were significantly increased(P＜0.05).Conclusion:ICA can inhibit the activity of the HMGB1/RAGE pathway,reduce the inflammatory response and tissue damage in AS rats,suppress osteoclast differentiation,and alleviate bone erosion.