National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University.
J Periodontol. 2016 May;87(5):e64-74. doi: 10.1902/jop.2015.150522. Epub 2015 Dec 8.
Clinical studies have showed that prediabetes (preDM) is a predisposing factor for periodontitis. However, the pathogenic mechanism involved is unclear. Because it is known that the activation of Toll-like receptor (TLR)-mediated nuclear factor-kappa B (NF-κB) signaling pathway plays a crucial role in periodontitis, it is hypothesized that preDM enhances periodontal inflammation by activation of the TLR-mediated NF-κB pathway.
In this study, a preDM rat model is established by feeding a high-fat diet (HFD). HFD-induced rats with preDM (n = 7) and normal chow-fed rats (n = 7) were studied. The animal model was characterized in terms of body weight and the glycemic and insulinemic profiles. The following parameters were assessed to evaluate possible early periodontal alterations and underlying mechanisms: 1) histology analysis of periodontal tissue; and 2) serum and mRNA levels and/or the tissue protein expression of TLRs, myeloid differentiation factor 88 (MyD88), tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), NF-κB, cytokines, advanced glucose ends (AGEs), and free fatty acids (FFAs).
Rats with preDM presented higher expression of TLR2 and TLR4 in periodontal tissue in the HFD group compared with the control group. The TLR2 and TLR4 was mostly expressed in gingiva, and TLR4 was expressed in periodontal ligament in rats. Furthermore, the MyD88 and TRAF6 protein levels were significantly increased in gingiva in rats with preDM compared with normal rats. The activity of NF-κB signals was higher in rats with preDM than in normal rats. Regarding cytokines expression, the TNF-α protein levels and interleukin-1β mRNA levels were significantly increased in the HFD group compared with the control group. In the serum, AGEs levels were significantly increased in the rats with preDM. Mean FFAs concentrations were increased in rats with preDM compared with normal rats, but it did not reach statistical significance.
In rats with preDM, TLR2 and TLR4 gene and protein levels were higher in periodontal tissue, and the activation of NF-κB may, through TLRs/MyD88, cause more cytokine secretion, which is associated with the onset or development of periodontal disease.
临床研究表明，糖尿病前期（preDM）是牙周炎的一个诱发因素。然而，其中涉及的发病机制尚不清楚。由于众所周知，Toll 样受体（TLR）介导的核因子-κB（NF-κB）信号通路的激活在牙周炎中起着至关重要的作用，因此假设 preDM 通过激活 TLR 介导的 NF-κB 通路增强牙周炎症。
本研究通过给予高脂肪饮食（HFD）建立 preDM 大鼠模型。研究了 HFD 诱导的 preDM 大鼠（n = 7）和正常饲料喂养的大鼠（n = 7）。根据体重和血糖及胰岛素谱特征对动物模型进行了描述。评估了以下参数，以评估可能的早期牙周改变和潜在机制：1）牙周组织的组织学分析；2）血清和 mRNA 水平和/或 TLRs、髓样分化因子 88（MyD88）、肿瘤坏死因子（TNF）受体相关因子 6（TRAF6）、NF-κB、细胞因子、晚期糖末端（AGEs）和游离脂肪酸（FFAs）的组织蛋白表达。
preDM 大鼠的牙周组织中 TLR2 和 TLR4 的表达高于对照组。TLR2 和 TLR4 主要在牙龈中表达，TLR4 在牙周韧带中表达。此外，preDM 大鼠牙龈中 MyD88 和 TRAF6 蛋白水平明显升高。preDM 大鼠 NF-κB 信号活性高于正常大鼠。关于细胞因子表达，HFD 组大鼠 TNF-α 蛋白水平和白细胞介素-1β mRNA 水平明显高于对照组。在血清中，preDM 大鼠的 AGEs 水平明显升高。与正常大鼠相比，preDM 大鼠的平均 FFAs 浓度升高，但差异无统计学意义。
在 preDM 大鼠中，牙周组织中 TLR2 和 TLR4 基因和蛋白水平升高，NF-κB 的激活可能通过 TLRs/MyD88 导致更多细胞因子的分泌，这与牙周病的发生或发展有关。
