基于TREM2/DAP12通路探讨小檗碱治疗牙周炎模型大鼠的作用机制OA

Objective:To investigate the therapeutic effects and potential mechanism of berberine on rat models of periodontitis.Methods:Rats were randomly divided into control group,model group and treatment group(n=6).Periodontitis model was established by silk ligation combined with lipopolysaccharide injection and high-fat and high-sugar diet in model group and treatment group.After successful modeling,the treatment group was given berberine suspension by gavage for 28 d,while the model group and control group were given the same volume of normal saline.Serum samples were collected before and after administration,and imaging examination and clinical periodontal probing were performed to evaluate inflammation and alveolar bone resorption.After treatment,bilateral gingival tissues were harvested and HE staining,immunohistochemical staining and tartrate-resistant acid phosphatase(TRAP)staining were used to observe histopathological changes.Differentially expressed genes were screened by RNA high-throughput sequencing.The expression levels of triggering receptor expressed on myeloid cells 2(TREM2)and DNAX activation protein 12(DAP12)were detected by Western blotting.RAW264.7 macrophages were stimulated with lipopolysaccharide or lipopolysaccharide combined with berberine,and intracellular reactive oxygen species levels were detected by immunofluorescence.Results:Compared with the model group,periodontal inflammation was significantly relieved in the treatment group,serum levels of TNF-α and IL-6 were decreased by 26.65%and 22.37%(P<0.05),and alveolar bone resorption was decreased by 29.72%(P<0.01).RNA high-throughput sequencing and Western blotting results showed that TREM2 expression was significantly up-regulated in the model group,which was reversed by berberine treatment(P<0.01).Compared with lipopolysaccharide treatment alone,the intracellular reactive oxygen species level of RAW264.7 macrophages treated with lipopolysaccharide combined with berberine was significantly decreased(P<0.01).Conclusion:Berberine can inhibit alveolar bone resorption caused by periodontitis and promote bone remodeling.The mechanism may be related to inhibiting the TREM2/DAP12 pathway and regulating osteoclast differentiation.