Periodontitis and Preterm Birth:Nonhuman Primate Model

牙周炎和早产：非人灵长类动物模型

• 批准号: 7054759
• 负责人: Jeffrey L Ebersole
• 金额: $ 48.49万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054759
• 关键词: animal birth weight; baboons; birth; dental plaque; dental research; disease /disorder model; disease /disorder proneness /risk; endotoxins; model design /development; newborn animals; nucleic acid hybridization; oral bacteria; pathologic process; periodontitis; premature infant animal; premature labor; radiography; tooth extraction

DESCRIPTION (provided by applicant): Current human epidemiologic reports indicate a positive association between preterm birth/low birth weight (PTB/LBW) neonates and periodontal disease prevalence in the mother. Sixty percent of infant mortality (not attributable to congenital/anatomical defects) is linked with PTB/LBW. It is the objective of this project to investigate potential mechanisms of the association between PTB/LBW and periodontitis in an in vivo model system. The baboon, Papio anubis, which has a >95 percent genetic homology to humans will be used to investigate Aims testing hypotheses that: (1) the incidence and severity of periodontitis results in an increased incidence of PTB/LBW neonates; (2) the progression of periodontitis is characterized by an increase in pathogenic subgingival microbial species and systemic expression of plaque pathogenicity, which correlate with an increased incidence of PTB/LBW neonates; and (3) the progression of periodontitis is characterized by local and systemic inflammatory biomarkers, which correlate with an increased incidence of PTB/LBW neonates. 400 female baboons, housed at the Southwest Foundation for Biomedical Research (SFBR), a NIH Regional Primate Center, will be randomized into two groups. Following baseline sample collection (blood, crevicular fluid (GCF), subgingival plaque, clinical assessment) from all baboons, ligature will be placed (one maxillary/one mandibular quadrant; 6 molar teeth) in the experimental group (n=200). Both groups will then be introduced to males. Pregnancy will be confirmed and gestational age determined using ultrasound at approximately 3 months. Oral samples will be collected at this time point, followed by placement of ligatures on the contralateral maxillary and mandibular quadrants of the experimental group to extend the exposure variable (i.e. periodontitis). Animals will be sampled at approximately 30 days following the completion of the pregnancy and ligatures removed. In both experimental and control groups, dates of birth and post-natal weights will be obtained within 14 days of birth. Blood IGCF samples will be assayed for acute phase reactants and endotoxin activity. Sera will also be analyzed for IgG antibody to oral microorganisms. Differences in clinical and laboratory parameters will be assessed between outcome (PTB/LBW vs. normal neonates) and between groups (experimental vs. control). Results from this investigation will describe mechanisms of this linkage and contribute to the development of therapeutic and clinical intervention strategies.

描述（由申请人提供）：当前人类流行病学报告 表明早产/低出生体重之间存在正相关 (PTB/LBW) 新生儿和母亲牙周病的患病率。六十 婴儿死亡率的百分比（不可归因于先天/解剖缺陷） 与 PTB/LBW 相关。该项目的目标是调查 PTB/LBW 与牙周炎之间关联的潜在机制 体内模型系统。狒狒 (Papio anubis) 的遗传率 >95% 与人类的同源性将用于调查目的测试假设：(1) 牙周炎的发病率和严重程度导致发病率增加 PTB/LBW 新生儿的比例； (2)牙周炎的进展特点是 致病性龈下微生物种类和全身表达的增加 斑块致病性，与 PTB/LBW 发病率增加相关 新生儿； (3)牙周炎的进展特点是局部 和全身炎症生物标志物，与增加相关 PTB/LBW 新生儿的发生率。 400 只雌性狒狒，饲养在西南部 NIH 地区灵长类动物中心生物医学研究基金会 (SFBR) 将 被随机分为两组。基线样本采集后（血液、 龈沟液（GCF）、龈下菌斑、临床评估） 狒狒，将进行结扎（一个上颌/一个下颌象限；6 实验组（n=200）中的臼齿）。随后两组将 介绍给男性。将确认怀孕并确定孕龄 大约3个月时使用超声波。口腔样本将采集于 这个时间点，然后在对侧进行结扎 实验组上颌和下颌象限延长 暴露变量（即牙周炎）。动物样本将在 怀孕和结扎完成后约 30 天 已删除。在实验组和对照组中，出生日期和产后 体重将在出生后 14 天内获得。 IGCF 血液样本将 测定急性期反应物和内毒素活性。塞拉也会 分析口腔微生物的 IgG 抗体。临床和临床上的差异 将在结果之间评估实验室参数（PTB/LBW 与正常 新生儿）和组间（实验与对照）。结果由此 调查将描述这种联系的机制并有助于 制定治疗和临床干预策略。