El-Shinnawi Una, Soory Mena
Periodontology, King' s College London Dental Institute, Denmark Hill, London SE5 9RW, UK.
Recent Pat Endocr Metab Immune Drug Discov. 2013 Sep;7(3):169-88. doi: 10.2174/18715303113139990040.
There is a significant prevalence of subjects with periodontitis presenting with other inflammatory conditions such as coronary heart disease, insulin resistance and arthritis. This pattern of disease presentation underscores the importance of inflammatory loading from chronic diseases, in driving their pathogeneses in a multidirectional manner. Pro-inflammatory cytokines and other agents play an important role in this process; for example, a single nucleotide polymorphism of the TNF-α gene is associated with significant periodontal attachment loss in patients with coronary heart disease. Changes in gene expression associated with inflammation and lipid metabolism in response to oral infection with the periodontal pathogen Porphyromonas gingivalis (Pg) have been demonstrated in mouse models, independent of the demonstration of atherosclerotic lesions. Insulin resistance is considered to be a chronic low-grade inflammatory condition, associated with altered glucose tolerance, hypertriglyceridemia, central obesity and coronary heart disease. It is accompanied by elevated levels of IL-1, IL-6 and TNF-α also relevant to the progression of periodontitis. There is evidence that uncontrolled periodontal disease contributes to maintenance of systemic diseases, including rheumatoid arthritis (RA), with increased risk of periodontitis in subjects with RA. The periodontal pathogen Pg is significant in contributing to citrullination of proteins resulting in immune dysregulation and autoimmune responses, seen in RA. However, they are both multifactorial chronic diseases with complex etiopathogeneses that affect their presentation. Consistent but weak associations are seen for surrogate markers of periodontitis such as tooth loss, with multiple systemic conditions. Effective treatment of periodontitis would be important in reducing systemic inflammatory loading from chronic local inflammation and in achieving systemic health. Lack of a consistent cause and effect relationship in all subjects would be influenced by genetic, epigenetic and other subject variables, although there are clear mechanisms that link the associations. This article includes an appraisal of patents and their applications.
患有牙周炎的患者同时伴有其他炎症性疾病，如冠心病、胰岛素抵抗和关节炎的情况相当普遍。这种疾病表现模式突显了慢性疾病的炎症负荷在多方向驱动其发病机制方面的重要性。促炎细胞因子和其他介质在这一过程中发挥着重要作用；例如，TNF-α基因的单核苷酸多态性与冠心病患者显著的牙周附着丧失有关。在小鼠模型中已证实，牙周病原体牙龈卟啉单胞菌（Pg）口腔感染后，与炎症和脂质代谢相关的基因表达会发生变化，而与动脉粥样硬化病变的表现无关。胰岛素抵抗被认为是一种慢性低度炎症状态，与葡萄糖耐量改变、高甘油三酯血症、中心性肥胖和冠心病有关。它还伴随着与牙周炎进展相关的IL-1、IL-6和TNF-α水平升高。有证据表明，未得到控制的牙周疾病会促使包括类风湿性关节炎（RA）在内的全身性疾病持续存在，RA患者患牙周炎的风险增加。牙周病原体Pg在导致蛋白质瓜氨酸化从而引发免疫失调和自身免疫反应方面具有重要作用，这在RA中可见。然而，它们都是病因复杂的多因素慢性疾病，会影响其表现。牙周炎的替代标志物如牙齿脱落与多种全身性疾病之间存在一致但较弱的关联。有效治疗牙周炎对于减少慢性局部炎症引起的全身性炎症负荷以及实现全身健康至关重要。尽管存在明确的关联机制，但在所有受试者中缺乏一致的因果关系会受到遗传、表观遗传和其他个体变量的影响。本文包括对专利及其应用的评估。
