PERIODONTITIS AND PRETERM BIRTH: NONHUMAN PRIMATE MODEL

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目前的人类流行病学报告表明，早产/低出生体重(PTB/LBW)新生儿与母亲牙周病患病率呈正相关。60%的婴儿死亡(不是由于先天性/解剖缺陷)与肺结核/LBW有关。本项目的目的是在活体模型系统中研究PTB/LBW与牙周炎之间的潜在联系机制。Papio Anubis与人类有95%的基因同源性，将被用来研究旨在检验假说的目标：(1)牙周炎的发生率和严重性导致PTB/LBW新生儿的发病率增加；(2)牙周炎的进展以致病的牙龈下微生物种类增加和菌斑致病性的系统表达为特征，这与PTB/LBW新生儿的发病率增加相关；(3)牙周炎的进展以局部和全身炎症生物标志物为特征，这些生物标志物与PLB/LBW新生儿的发病率增加有关。美国国立卫生研究院区域灵长类动物中心西南生物医学研究基金会(SFBR)饲养了400只雌性狒狒，它们将被随机分为两组。实验组(n=200)在采集基线样本(血液、龈沟液(GCF)、龈下菌斑、临床评估)后，放置结扎器(上颌/下颌象限各1颗；磨牙6颗)。然后，这两组动物都将被介绍给雄性。将在大约3个月时使用超声波确认怀孕并确定孕周。在这个时间点采集口腔样本，然后在实验组的对侧上颌象限放置结扎器，以扩大暴露变量(即牙周炎)。动物将在妊娠完成后约30天内进行抽样，并摘除结扎线。在试验组和对照组中，出生日期和出生后体重都将在出生后14天内获得。将对血液IGCF样本进行急性期反应物和内毒素活性检测。还将分析血清中对口腔微生物的抗体。临床和实验室参数的差异将在结局(PTB/LBW与正常新生儿)和两组之间(试验组与对照组)之间进行评估。这项研究的结果将描述这种联系的机制，并有助于治疗和临床干预策略的发展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 increase 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 increase 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 PLB/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 experiment 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 weight 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.