| Objective Exploring the molecular mechanism of You Gui Wan (YGW) in inhibiting the inflammatory response of articular cartilage tissue in knee osteoarthritis (KOA) model based on high mobility group box1(HMGB1)/advanced glycation end product receptor (RAGE) /nuclear factor-κB (NF-κB) signaling pathway. Methods Sixty Sprague-Dawley rats were randomly divided into sham operation (SHAM) group, model (KOA)group, You Gui Wan low dose (KOA+YGWL) group, You Gui Wan medium dose (KOA+YGWM) group, You Gui Wan high dose (KOA+YGWH) group, positive control group of glucosamine sulfate (KOA+GS) group. Correspondence drug was intragastric administration in 6 weeks after modeling, samples were taken 8 weeks after intragastric administration, various techniques including Safranin O solid green staining, ELISA method, RT-PCR and Western blot were used to assess articular cartilage tissue morphology, changes of inflammatory cytokine levels in the serum, changes of HMGB1, RAGE, NF-κB gene and protein expression in the articular cartilage tissue. Results Our results suggest that the degree of joint cartilage injury, OARSI score, OARSI score, serum PGE2 levels, and expression of RAGE and NF-κB proteins in knee cartilage tissue were significantly lower in the KOA+YGWM group, KOA+YGWH group, KOA+GS group than that in the KOA group, the levels of IL-18, COX2 in the KOA+YGWL group, KOA+ YGWM group, KOA+YGWH group, KOA+GS group were also significantly lower than that in the KOA group, as well as reduced gene expression of HMGB1, RAGE, and NF-κB in articular cartilage tissue, along with decreased HMGB1 protein expression (P<0.05 or P<0.01). The study results showed that the degree of joint cartilage injury, OARSI score, HMGB1 gene expression, and NF-κB and HMGB1 protein expression in articular cartilage tissue were significantly higher in the KOA+YGWL group than that in the KOA+ GS group, the gene expressions of RAGE, NF-κB and the RAGE protein expression were also significantly higher in the KOA+YGWL group, KOA+YGWM group than that in the KOA+GS group, yet the gene expressions of RAGE, NF-κB were significantly lower in the KOA+YGWH group than that in the KOA+GS group (P<0.01). Conclusion You Gui Wan can alleviate joint cartilage tissue damage in KOA model, and its mechanism is closely related to inhibiting the secretion of downstream inflammatory factors of the HBGB1/RAGE/NF-κB signaling pathway, thereby suppressing the inflammatory response. |