The Role of Stress Induced Hypoxia in Periodontitis

项目概述牙周病是世界上导致牙齿脱落的主要原因之一。虽然已知心理压力会加重牙周病理，但确切的机制仍有待阐明。我们实验室的研究表明，在皮肤伤口愈合过程中，心理压力会减少可用氧气，增加机会性细菌。应激动物的高氧治疗能够将愈合恢复到控制水平。先前的研究也表明牙周炎期间组织氧合减少，高压氧治疗对其治疗有益。较低的组织氧水平可能会降低免疫潜能，并有利于与牙周病理相关的厌氧细菌的生长。大约30%的美国成年人患有牙周病，压力比以往任何时候都更普遍，了解这种联系是很重要的。因此，我们研究的长期目标是阐明心理应激下牙周病理的分子机制。本研究旨在探讨组织氧合改变在牙周病理中的作用。我们的中心假设是，心理压力通过减少牙周组织中的氧气可用性而增加牙周病理。我们打算用牙周炎大鼠模型来研究我们的假设。我们的目的是确定：1)心理应激降低牙周组织的伤口氧合，2)通过高氧治疗恢复缺氧牙周组织的氧合，是否会减轻应激对牙周炎的影响。组织缺氧将通过免疫组织化学使用缺氧标志物（吡莫硝唑）进行评估，并与缺氧诱导因子（HIF）激活的研究相证实。这些值将与各自组织的牙周状况相关。正如我们之前创伤愈合受损的应激炎症模型，我们期望通过恢复组织的氧合来减少牙周病理。更好地了解压力在牙周病中的作用将有助于加强现有的治疗方式，并指导基于证据的患者护理替代方案。未来的研究将计划调查氧调节酶和基因的作用，以及糖皮质激素和儿茶酚胺能途径。这将使我们对压力如何影响牙周病的机制有新的认识。

DESCRIPTION (provided by applicant): Project Summary Periodontal disease is one of the major causes of tooth loss in the world. Although psychological stress is known to aggravate periodontal pathology, the exact mechanisms remain to be elucidated. Studies from our laboratory have shown that psychological stress decreases available oxygen and increases opportunistic bacteria during cutaneous wound healing. Hyperoxia therapy in the stressed animals was able to restore healing to control levels. Previous studies have also shown decreased oxygenation of the tissues during periodontitis, and hyperbaric oxygen therapy to be of benefit in its treatment. Lower tissue oxygen levels could decrease immune potential, and favor the growth of anaerobic bacteria that have been associated with periodontal pathology. With approximately 30% of the adult US population suffering from periodontal disease, and with stress more prevalent than ever, understanding this association is important. Hence, the long-term goal of our study is to elucidate the molecular mechanisms underlying periodontal pathology in psychological stress. This proposal aims to explore the role of altered tissue oxygenation in periodontal pathology. Our central hypothesis is that psychological stress increases periodontal pathology by decreasing oxygen availability in the periodontal tissues. We intend to study our hypothesis using a rat model of periodontitis. Our objectives are to determine if: 1) psychological stress decreases wound oxygenation in periodontal tissues and 2) restoring oxygenation to the hypoxic periodontal tissues, by hyperoxia therapy, would alleviate the effects of stress on periodontitis. Tissue hypoxia will be evaluated by immunohistochemistry using a hypoxia marker (pimonidazole), and corroborated with studies of hypoxia inducible factor (HIF) activation. These values will be correlated to the periodontal status of the respective tissues. As with our previous stress-inflammatory model of impaired wound healing, we anticipate to decrease periodontal pathology by restoring oxygenation to the tissues. A better understanding of the role of stress in periodontal disease will help enhance existing treatment modalities, and guide evidence based alternatives for patient care. Future studies will plan to investigate the role of oxygen regulated enzymes and genes, as well as glucocorticoid and catecholaminergic pathways. This will give us new insight into the mechanisms of how stress affects periodontal disease. Project Narrative: Periodontal disease is one of the major causes of tooth loss in the world. Psychological stress is known to increase the severity of periodontal disease. In this proposal, we explore the role of decreased tissue oxygenation in periodontal pathology in the context of stress. Results from these studies will provide valuable insight into the role of oxygen in stress-induced periodontal pathology and its ability to ameliorate it, leading to future studies in oxygen regulated pathways. The insights gain will help take our findings from the bench to the clinics, and to develop novel strategies to improve healing and promote periodontal health.