Breivik Torbjørn, Gundersen Yngvar, Osmundsen Harald, Fonnum Frode, Opstad Per Kristian
Department of Periodontology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
J Periodontal Res. 2006 Feb;41(1):23-32. doi: 10.1111/j.1600-0765.2005.00833.x.
The responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis has been found to play a significant role for susceptibility and resistance to periodontal disease. In the present study we have investigated the effects of two different treatment strategies, which have been found to down-regulate the HPA axis, on ligature-induced periodontitis.
In experiment 1, newborn rats were treated with the synthetic glucocorticoid hormone dexamethasone-21-phosphate, which permanently down-regulates HPA axis responsiveness. In experiment 2, adult rats were treated with the novel antidepressant drug tianeptine, which opposes the action of stress. Periodontitis was inflicted upon all rats. Just before decapitation the animals received gram-negative bacterial lipopolysaccharide (LPS) to induce a robust immune and HPA axis response.
Compared to the saline-treated control rats, dexamethasone-treated rats had significantly less periodontal bone loss (p < 0.01), reduced expression of glucocorticoid receptors in the hippocampus (p < 0.001), lower corticosterone (p=0.01) and higher plasma levels of the cytokine tumor necrosis factor (TNF)-alpha (p < 0.05) after LPS challenge. Also the tianeptine-treated rats showed significantly reduced periodontal bone loss (p=0.01), enhanced plasma levels of TNF-alpha (p < 0.05), and transforming growth factor-1beta (p < 0.01), whereas no significant difference was found in corticosterone levels.
An individual's responsiveness to danger signals, whether they are of immunological, chemical, or psychological origin, may be an important factor for explaining variability in susceptibility to periodontal disease. The results may provide new insight into the mechanisms of periodontal disease development, and open new vistas for disease prevention.
已发现下丘脑 - 垂体 - 肾上腺（HPA）轴的反应性在牙周病易感性和抵抗力方面发挥重要作用。在本研究中，我们调查了两种已发现可下调HPA轴的不同治疗策略对结扎诱导的牙周炎的影响。
在实验1中，新生大鼠用合成糖皮质激素磷酸地塞米松 - 21进行治疗，其可永久性下调HPA轴反应性。在实验2中，成年大鼠用新型抗抑郁药噻奈普汀进行治疗，其可对抗应激作用。所有大鼠均诱发牙周炎。在断头前，动物接受革兰氏阴性菌脂多糖（LPS）以诱导强烈的免疫和HPA轴反应。
与盐水处理的对照大鼠相比，地塞米松处理的大鼠在LPS攻击后牙周骨丢失明显更少（p < 0.01），海马中糖皮质激素受体表达降低（p < 0.001），皮质酮水平更低（p = 0.01），细胞因子肿瘤坏死因子（TNF） - α的血浆水平更高（p < 0.05）。噻奈普汀处理的大鼠也显示牙周骨丢失明显减少（p = 0.01），TNF - α（p < 0.05）和转化生长因子 - 1β（p < 0.01）的血浆水平升高，而皮质酮水平未发现显著差异。
个体对危险信号的反应性，无论其源于免疫、化学还是心理因素，可能是解释牙周病易感性差异的重要因素。这些结果可能为牙周病发展机制提供新的见解，并为疾病预防开辟新的前景。
