Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas, PPGMCF, SBFis, Department of Basic Sciences, School of Dentistry, São Paulo State University (UNESP), Araçatuba, Brazil.
Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (UNESP), Araçatuba, Brazil.
Int Endod J. 2021 Jun;54(6):926-940. doi: 10.1111/iej.13474. Epub 2021 Jan 27.
To verify the effects of melatonin supplementation on insulin sensitivity, plasma concentrations of inflammatory cytokines, insulin signalling and inflammatory pathways in the soleus (SM) and extensor digitorum longus (EDL) muscles of rats with apical periodontitis (AP).
Seventy-two Wistar rats were distributed into 4 groups: (a) control (C), (b) control supplemented with melatonin (M), (c) AP (AP), and (d) AP supplemented with melatonin (AP + M). AP was induced by pulp exposure of the maxillary and mandibular right first and second molars to the oral environment. After AP induction, oral supplementation with 5 mg kg melatonin (diluted in drinking water) for 60 days was initiated. At the end of the treatment, the following were analysed: (1) plasma concentrations of insulin and inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10) using ELISA kits; (2) glycaemia using enzymatic assay; (3) insulin resistance using homoeostasis model assessment of insulin resistance (HOMA-IR) index; and (4) phosphorylation status of pp185 tyrosine, Akt serine, IKKα/β, and JNK in SM and EDL using Western blot. Analysis of variance of two or three factors was performed, followed by the Bonferroni test. P values < 0.05 were considered statistically significant.
AP promoted insulin resistance, significantly increased (P < 0.05) plasma concentrations of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), significantly decreased (P < 0.05) the concentration of anti-inflammatory cytokine IL-10, impaired insulin signalling in SM, and increased IKKα/β phosphorylation status in SM and EDL. Melatonin supplementation in rats with AP improved insulin sensitivity, significantly decreased (P < 0.05) TNF-α and IL-1β, significantly increased (P < 0.05) IL-10 plasma concentrations, and changed the insulin signalling in soleus muscle and IKKα/β phosphorylation status in SM and EDL muscles.
Melatonin is a potent adjuvant treatment for improving apical periodontitis-associated changes in insulin sensitivity, insulin signalling and inflammatory pathways. In addition, the negative impact of AP on general health was also demonstrated.
验证褪黑素补充对根尖周炎大鼠比目鱼肌和伸趾长肌胰岛素敏感性、炎症细胞因子血浆浓度、胰岛素信号转导和炎症途径的影响。
将 72 只 Wistar 大鼠分为 4 组：（a）对照组（C）、（b）对照组加褪黑素（M）、（c）根尖周炎组（AP）和（d）根尖周炎加褪黑素（AP+M）。通过暴露上颌和下颌右侧第一和第二磨牙的牙髓到口腔环境来诱导 AP。AP 诱导后，开始口服补充 5mgkg 褪黑素（溶于饮用水中）60 天。治疗结束时，分析以下指标：（1）使用 ELISA 试剂盒测定血浆胰岛素和炎症细胞因子（TNF-α、IL-6、IL-1β 和 IL-10）浓度；（2）用酶法测定血糖；（3）用稳态模型评估的胰岛素抵抗指数（HOMA-IR）评估胰岛素抵抗；（4）用 Western blot 测定比目鱼肌和伸趾长肌中 pp185 酪氨酸、Akt 丝氨酸、IKKα/β 和 JNK 的磷酸化状态。进行两因素或三因素方差分析，然后进行 Bonferroni 检验。P 值<0.05 为差异有统计学意义。
AP 导致胰岛素抵抗，显著增加（P<0.05）促炎细胞因子（TNF-α、IL-6 和 IL-1β）的血浆浓度，显著降低（P<0.05）抗炎细胞因子 IL-10 的浓度，损害比目鱼肌的胰岛素信号转导，并增加比目鱼肌和伸趾长肌 IKKα/β 的磷酸化状态。AP 大鼠补充褪黑素可改善胰岛素敏感性，显著降低（P<0.05）TNF-α和 IL-1β，显著增加（P<0.05）IL-10 的血浆浓度，并改变比目鱼肌的胰岛素信号转导和 IKKα/β 在比目鱼肌和伸趾长肌中的磷酸化状态。
褪黑素是一种有效的辅助治疗方法，可改善根尖周炎相关的胰岛素敏感性、胰岛素信号转导和炎症途径的变化。此外，还证明了 AP 对整体健康的负面影响。
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