AimTo establish a reproducible experimental animal model for systemic lupus erythematosus (SLE)‐associated periodontitis (PD), investigate the effects of SLE on PD and assess the therapeutic potential of alpha‐ketoglutarate (αKG) for SLE‐PD treatment.Materials and MethodsAn SLE‐PD murine model was established via ligature‐induced PD in MRL‐lpr strain, with MRL/MpJ strain as a non‐SLE control. The periodontal state was assessed using micro‐CT, real‐time PCR, histology, immunofluorescence and flow cytometry assays. αKG levels were analysed, and a thermoresponsive gel was designed as a periodontal dimethyl (DM)‐αKG delivery system. αKG levels were analysed in gingival crevicular fluid (GCF) of PD patients with or without SLE.ResultsSLE significantly increased the periodontal inflammation and bone resorption in the SLE‐PD model. αKG levels in GCF were lower in PD patients with SLE than in PD patients without SLE. Decreased αKG levels in the gingiva and macrophage M1/M2 imbalance were observed in SLE‐PD mice. However, DM‐αKG thermoresponsive gel effectively alleviated the periodontal inflammation, bone resorption and macrophage M1/M2 imbalance in SLE‐PD mice.ConclusionsOur study established, for the first time, a novel SLE‐PD murine model and revealed that SLE increases the severity of PD in vivo. Our findings highlight the therapeutic potential of αKG for SLE‐associated PD.

中文翻译：

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α-酮戊二酸在新型小鼠模型中减轻系统性红斑狼疮相关牙周炎


目的建立系统性红斑狼疮 （SLE） 相关牙周炎 （PD） 的可重复实验动物模型，研究 SLE 对 PD 的影响，并评估 α-酮戊二酸 （αKG） 治疗 SLE-PD 的治疗潜力。材料和方法在 MRL-lpr 菌株中通过结扎诱导的 PD 建立 SLE-PD 小鼠模型，以 MRL/MpJ 菌株作为非 SLE 对照。使用 micro-CT 、实时 PCR、组织学、免疫荧光和流式细胞术测定评估牙周状态。分析 αKG 水平，并将热反应凝胶设计为牙周二甲基 （DM）‐αKG 递送系统。分析伴或不伴 SLE 的 PD 患者牙龈沟液 （GCF） 中的 αKG 水平。结果SLE 显著增加了 SLE-PD 模型中的牙周炎症和骨吸收。SLE 的 PD 患者 GCF 中的 αKG 水平低于无 SLE 的 PD 患者。在 SLE-PD 小鼠中观察到牙龈中 αKG 水平降低和巨噬细胞 M1/M2 失衡。然而，DM-αKG 热反应凝胶有效缓解了 SLE-PD 小鼠的牙周炎症、骨吸收和巨噬细胞 M1/M2 失衡。结论我们的研究首次建立了一种新的 SLE-PD 小鼠模型，并揭示了 SLE 在体内增加了 PD 的严重程度。我们的研究结果强调了 αKG 治疗 SLE 相关 PD 的潜力。