Breivik Torbjørn, Gundersen Yngvar, Opstad Per Kristian, Fonnum Frode
Department of Periodontology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
J Periodontal Res. 2005 Aug;40(4):325-30. doi: 10.1111/j.1600-0765.2005.00803.x.
The responsiveness of the sympathetic nervous system (SNS) and the hypothalamic--pituitary--adrenal (HPA) axis plays a major role in immune regulation and for the outcome of infections and inflammatory disorders. This study was designed to investigate whether chemical SNS denervation with the noradrenaline-selective neurotoxic drug 6-hydroxydopamine (6-OHDA), which destroys peripheral noradrenaline terminals, would influence immune responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation, and the progression of ligature-induced periodontal disease in Fischer 344 rats.
6-OHDA (40--60 microg/kg) or vehicle was injected intraperitoneally (i.p.) on days 1, 3 and 5, 10 days before application of the ligatures, and thereafter weekly in doses of 80 microg/kg. Periodontal disease was assessed when the ligatures had been in place for 49 days. At 24 and 2 h before decapitation, all rats received LPS (150 microg/kg i.p.) to induce a robust immune and HPA axis response.
The 6-OHDA-treated rats showed significantly reduced bone loss as measured by digital X-rays (p< 0.01), and enhanced levels of the cytokines transforming growth factor-beta (p=0.05) and interleukin-6 (p=0.05), as well as the HPA axis derived hormone corticosterone (p=0.01), induced by LPS stimulation.
6-OHDA-induced chemical sympathectomy inhibits ligature-induced periodontal disease in this model. This effect may be attributable to the well-documented ability of the SNS to regulate immune system function primarily via the adrenergic neurotransmitter noradrenaline released at sympathetic nerve terminals. The enhanced HPA axis activation may be a compensatory response that reduces the T helper (Th)2 to Th1 skewing effect of treatment with 6-OHDA.
交感神经系统（SNS）和下丘脑 - 垂体 - 肾上腺（HPA）轴的反应性在免疫调节以及感染和炎症性疾病的转归中起主要作用。本研究旨在调查用去甲肾上腺素选择性神经毒性药物6 - 羟基多巴胺（6 - OHDA）进行化学性SNS去神经支配（其可破坏外周去甲肾上腺素能末梢）是否会影响对革兰氏阴性菌脂多糖（LPS）刺激的免疫反应，以及对Fischer 344大鼠结扎诱导的牙周病进展的影响。
在结扎前10天的第1、3和5天腹腔注射（i.p.）6 - OHDA（40 - 60μg/kg）或赋形剂，此后每周注射剂量为80μg/kg。在结扎49天后评估牙周病情况。在断头前24小时和2小时，所有大鼠接受LPS（150μg/kg i.p.）以诱导强烈的免疫和HPA轴反应。
通过数字X射线测量，6 - OHDA处理的大鼠骨丢失明显减少（p < 0.01），并且LPS刺激诱导的细胞因子转化生长因子 - β（p = 0.05）和白细胞介素 - 6（p = 0.05）以及HPA轴衍生激素皮质酮（p = 0.01）水平升高。
在该模型中，6 - OHDA诱导的化学性交感神经切除术可抑制结扎诱导的牙周病。这种作用可能归因于SNS主要通过交感神经末梢释放的肾上腺素能神经递质去甲肾上腺素来调节免疫系统功能这一已被充分证明的能力。增强的HPA轴激活可能是一种代偿反应，可减少6 - OHDA治疗引起的辅助性T细胞（Th）2向Th1的偏移效应。
