Lu Huaixiu, Xu Minguang, Wang Feng, Liu Shisen, Gu Jing, Lin Songshan
Department of Stomatology, Navy General Hospital, Beijing, China.
Department of Medical Engineering, The Second Artillery General Hospital of PLA, Beijing, China.
Exp Mol Med. 2014 Oct 17;46(10):e118. doi: 10.1038/emm.2014.65.
This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.
本研究评估了慢性应激（CS）在刺激交感神经系统中的作用，并探讨了牙周炎的潜在机制。使用牙周炎和CS的动物模型，评估了酪氨酸羟化酶（TH）的表达以及α1-肾上腺素能受体（α1-AR）和β2-肾上腺素能受体（β2-AR）的蛋白水平。此外，用人牙周膜成纤维细胞（HPDLFs）进行脂多糖（LPS）刺激以模拟炎症过程。评估了HPDLFs的增殖以及α1-AR和β2-AR的表达。在体外和体内用α1/β2-AR阻滞剂酚妥拉明/普萘洛尔预处理后，检测炎症相关细胞因子白细胞介素（IL）-1β、IL-6和IL-8。结果显示，CS条件下的牙周炎增强了TH、α1-AR和β2-AR的表达。酚妥拉明显著降低了炎症细胞因子水平。此外，我们观察到LPS预处理后HPDLF增殖显著降低以及α1-AR表达增加。酚妥拉明预处理显著改善了LPS抑制的细胞增殖。此外，阻断α1-AR信号也阻碍了炎症相关细胞因子IL-1β、IL-6和IL-8的上调。这些结果表明，CS可通过α1-肾上腺素能信号介导的炎症反应显著增强牙周炎的病理进展。我们已经确定了一种治疗牙周疾病的潜在治疗靶点，特别是在那些同时患有CS的患者中。
