The Role of Stress Induced Hypoxia in Periodontitis

压力引起的缺氧在牙周炎中的作用

• 批准号: 7468916
• 负责人: PRAVEEN GAJENDRAREDDY
• 金额: $ 7.85万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-20 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7468916
• 关键词: Adrenergic alpha-Antagonists; Adult; Affect; Anaerobic Bacteria; Animals; Antioxidants; Bacteria; Blood; Blood Vessels; Blood flow; Catecholamines; Clinic; Collagen; Communicable Diseases; Cutaneous; Disease; Enzyme Gene; Floods; Fusobacterium nucleatum; Future; Gene Expression; Genes; Glucocorticoids; Goals; Growth; Healed; Health; Hyperbaric Oxygenation; Hyperoxia; Hypochlorous Acid; Hypochlorous Acids; Hypoxia; Hypoxia Inducible Factor; Immune; Immune response; Immunohistochemistry; Impaired wound healing; Infection; Inflammation; Inflammatory; Laboratories; Lasers; Leukocytes; Ligature; Measurement; Measures; Mediating; Modality; Modeling; Molecular; Mus; Numbers; Opportunistic Infections; Oral; Oxygen; Pathogenesis; Pathology; Pathway interactions; Patient Care; Periodontal Diseases; Periodontitis; Peripheral; Peroxides; Phentolamine; Pimonidazole; Play; Polymerase Chain Reaction; Population; Porphyromonas gingivalis; Psychological Models; Psychological Stress; Rattus; Research; Ribosomal RNA; Risk; Role; Root Scaling; Severities; Spectrum Analysis; Stress; Structure; Superoxide Dismutase; Sympathetic Nervous System; Testing; Therapeutic; Tissues; Tooth Loss; Vascular Endothelial Growth Factors; Vascular blood supply; Vasomotor; Wound Healing; azomycin; bactericide; base; catalase; density; healing; human NOS2A protein; hypoxia inducible factor 1; imidazoline receptors; improved; insight; novel strategies; response; rilmenidine; tissue oxygenation; vasoconstriction; wound

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.

描述（由申请人提供）：项目摘要牙周病是世界上牙齿脱落的主要原因之一。虽然心理压力会加重牙周病，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并增加机会性细菌。对应激动物进行高氧治疗能够将愈合恢复到控制水平。以前的研究也表明，牙周炎期间组织的氧合减少，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力，并有利于与牙周病理学相关的厌氧菌的生长。由于大约30%的美国成年人患有牙周病，并且压力比以往任何时候都更加普遍，因此了解这种关联非常重要。因此，我们的长期研究目标是阐明心理应激下牙周病理学的分子机制。这项建议的目的是探讨牙周病理改变组织氧合的作用。我们的中心假设是，心理压力增加牙周组织中的氧可用性降低牙周病理。我们打算用大鼠牙周炎模型来研究我们的假设。我们的目标是确定：1）心理应激是否会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。将使用缺氧标记物（哌莫硝唑）通过免疫组织化学评价组织缺氧，并与缺氧诱导因子（HIF）活化研究相证实。这些值将与相应组织的牙周状态相关。与我们以前的创伤愈合受损的应激-炎症模型一样，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，并为患者护理提供基于证据的替代方案。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。 项目叙述：牙周病是世界上牙齿脱落的主要原因之一。牙周病的危害有哪些？在这个建议中，我们探讨了在压力的背景下，牙周病理组织氧合减少的作用。这些研究的结果将提供有价值的洞察力的作用，氧在应力诱导的牙周病理及其改善它的能力，导致未来的研究在氧调节途径。获得的见解将有助于将我们的发现从实验室带到诊所，并制定新的策略来改善愈合和促进牙周健康。