Multicenter Post-Graduate Program in Physiological Sciences (SBFis), Department of Basic Sciences, School of Dentistry, São Paulo State University (UNESP), Araçatuba, Brazil.
Department of Child and Social Dentistry, School of Dentistry, São Paulo State University (UNESP), Araçatuba, Brazil.
J Periodontol. 2019 Aug;90(8):884-893. doi: 10.1002/JPER.18-0568. Epub 2019 Feb 21.
Maternal periodontal disease leads to low birth weight (LBW), insulin resistance (IR), increased TNF-α levels, and alterations in insulin signaling in adult offspring. TNF-α has been associated with the stimulation of IKKβ/NF-κB, resulting in the decreased expression of GLUT4. Another mechanism that may be involved in decreasing GLUT4 expression is DNA methylation. This study aimed to evaluate in the adult offspring of rats with periodontal disease: IR, inflammatory pathways, DNA methylation, and expression of GLUT4.
Female Wistar rats were distributed into control and experimental periodontal disease groups. Seven days after induction of periodontal disease, both groups were mated with healthy male rats. After weaning, male offspring were distributed into control offspring (CN-o) and periodontal disease offspring (PED-o) groups. Body weights were measured from 0-75 days of age. At day 75, the following were measured in the offspring: IR (HOMA-IR index); TNF-α and NF-κBp65 content in the gastrocnemius muscle (GM) by western blotting; IKKα/β, JNK, ERK 1/2, NF-κBp65, and NF-κBp50 phosphorylation status in the GM by western blotting; DNA methylation by restriction digest and real-time PCR(qAMP); and expression of GLUT4 mRNA in the GM by real-time PCR.
LBW, IR, increases in TNF-α, IKKα/β, ERK 1/2, NF-κBp65, and NF-κBp50 decreased expression of GLUT4 mRNA were observed in the PED-o rats. No differences were identified in JNK phosphorylation status and DNA methylation in the evaluated regions of the GLUT4-encoding gene Slc2a4.
Maternal periodontal disease causes LBW, IR, activation of inflammatory pathways, and decreased GLUT4 expression in the GM of adult offspring.
母体牙周病可导致低出生体重(LBW)、胰岛素抵抗(IR)、TNF-α 水平升高以及成年后代胰岛素信号转导改变。TNF-α 与 IKKβ/NF-κB 的刺激有关,导致 GLUT4 的表达减少。另一种可能参与降低 GLUT4 表达的机制是 DNA 甲基化。本研究旨在评估牙周病大鼠的成年后代:IR、炎症通路、DNA 甲基化和 GLUT4 表达。
将雌性 Wistar 大鼠分为对照组和牙周病实验组。牙周病诱导 7 天后,两组均与健康雄性大鼠交配。断乳后,雄性后代分为对照组后代(CN-o)和牙周病后代(PED-o)组。从 0 到 75 天测量体重。在第 75 天,测量后代的以下指标:IR(HOMA-IR 指数);通过 Western 印迹法测量腓肠肌(GM)中的 TNF-α 和 NF-κBp65 含量;GM 中 IKKα/β、JNK、ERK 1/2、NF-κBp65 和 NF-κBp50 的磷酸化状态通过 Western 印迹法测定;通过限制消化和实时 PCR(qAMP)测定 DNA 甲基化;GM 中 GLUT4 mRNA 的表达通过实时 PCR 测定。
PED-o 大鼠出现 LBW、IR、TNF-α 增加、IKKα/β、ERK 1/2、NF-κBp65 和 NF-κBp50 表达减少,GLUT4 mRNA 表达降低。在评估的 GLUT4 编码基因 Slc2a4 区域未发现 JNK 磷酸化状态和 DNA 甲基化的差异。
母体牙周病导致 LBW、IR、炎症途径激活以及成年后代 GM 中 GLUT4 表达降低。