Abstract: Objective: To explore the role of macrophage polarization in apical periodontitis complicated with diabetes mellitus and the effect of high glucose environment on macrophage polarization. Methods: Eight-week-old male Wistar rats (control group) and GK rats (diabetes group) were used to construct the apical periodontitis model, and samples were taken at 2 weeks and 4 weeks. Hematoxylin-eosin (HE) staining was used to observe the infiltration of periapical inflammation. The expression of inflammatory cytokines was visualized by immunohistochemical staining. Immunofluorescence staining was used to evaluate the polarization of macrophages. Raw264.7 mouse macrophage lines were cultured in vitro and treated with high concentration of glucose (40 mM). Quantitative real-time PCR was used to detect the mRNA expression of iNOS, CD206, CD68, IL-1β, IL-6, TNF-α, and IL-10. Results: After 4 weeks, apical inflammatory infiltration in the diabetic group was significantly higher than that in the control group. Immunohistochemical staining showed that the expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 increased in the diabetic group, while the expression of anti-inflammatory cytokines IL-10 decreased in the diabetic group (P<0.05). The ratio of M2 macrophages to total macrophages in the diabetic group (CD206/CD68) was lower than that in the control group, and the expression of iNOS in macrophages as well as the number of apoptotic cells were both increased (P<0.05). In vitro, the mRNA expression of iNOS increased while CD206 decreased, and there was no significant difference in the mRNA expression of CD68. The level of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 ascended, and anti-inflammatory cytokines IL-10 descended (P<0.05). Conclusion: Diabetes-induced hyperglycemia can affect macrophage polarization and inflammatory cytokines secretion, which may further aggravate periapical periodontitis

Key words: apical periodontitis, diabetes, macrophage polarization