Effect of Metformin on Inflammatory Response in Periodontitis Mice by Regulating the TLR4/NF-κB Signaling Pathway
This study aims to investigate the effect of MET(metformin)on the inflammatory response in periodontitis mice by regulating the TLR4(Toll-like receptor 4)/NF-κB(nuclear factor-κB)signaling pathway.A periodontitis mouse model was constructed and the mice were separated into Control group,Model group,low,medium,and high dose metformin groups(MET-L group,MET-M group,MET-H group),and high-dose metformin+TLR4 activator group(MET-H+LPS group).The pathological changes of periodontal tissue in mice were observed by Micro-CT and HE staining.The mRNA expression levels of IL-1β(interleukin-1β),IL-6(inter-leukin-6),and TNF-α(tumor necrosis factor-α)in periodontal tissue were detected by qRT-PCR.The expression of RANKL(receptor activator of nuclear factor-κB ligand)and OPG(osteoprotegerin)in periodontal tissue was detected by immunohistochemistry.The expression of TLR4/NF-κB pathway-associated proteins was detected by Western blot.Compared with the Control group,the alveolar bone of mice in the Model group showed ob-vious absorption,with a larger bone absorption area,more severe periodontal lesions,and a large amount of inflammatory cell infiltration;the IL-1β,IL-6,TNF-α mRNA,and TLR4,p-NF-κB/NF-κB,RANKL expression levels increased,while OPG expression level decreased(P＜0.05).Compared with the Model group,the MET-L,MET-M,and MET-H groups showed a gradual decrease in alveolar bone resorption,reduced infiltration of inflammatory cells,and gradual relief of periodontal lesions;the TNF-α,IL-6,and IL-1β mRNA levels gradually decreased in a dose-dependent manner,the TLR4,p-NF-κB/NF-κB,and RANKL expression levels decreased,while the OPG expression level increased(P＜0.05).Compared with the MET-H group,the MET-H+LPS group showed increased alveolar bone resorption,larger bone resorption areas,and more inflammatory cell infiltration;the TNF-α,IL-6,IL-1β mRNA,and TLR4,p-NF-κB/NF-κB,RANKL expression levels increased,while OPG expression level decreased(P＜0.05).Metformin inhibits the TLR4/NF-κB signaling pathway and improves the inflammatory response in periodontitis mice.
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