PERIODONTITIS AND PRETERM BIRTH: NONHUMAN PRIMATE MODEL

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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%的婴儿死亡率（非先天性/解剖缺陷所致）与PTB/LBW有关。本项目的目的是在体内模型系统中研究PTB/LBW与牙周炎之间的相关性的潜在机制。狒狒，Papio anubis，与人类有95%的遗传同源性，将用于研究目的检验假设：（1）牙周炎的发病率和严重程度导致PTB/LBW新生儿发病率增加;（2）牙周炎的进展的特征在于致病性龈下微生物种类的增加和菌斑致病性的系统性表达，其与PTB/LBW新生儿发病率的增加相关;和（3）牙周炎的进展以局部和全身炎症生物标志物为特征，其与PLB/LBW新生儿发病率的增加相关。400只雌性狒狒，被安置在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），将被随机分为两组。从所有狒狒采集基线样本（血液、龈沟液（GCF）、龈下菌斑、临床评估）后，在实验组（n=200）中放置结扎线（一个上颌/一个下颌象限; 6颗臼齿）。然后将这两组动物介绍给雄性动物。在大约3个月时，将使用超声确认妊娠并确定胎龄。将在该时间点采集口腔样本，然后在实验组的对侧上颌和下颌象限上放置结扎线，以扩展暴露变量（即牙周炎）。将在妊娠完成后约30天对动物进行采样，并去除结扎线。在实验组和对照组中，将在出生后14天内获得出生日期和出生后体重。将测定血液IGCF样本的急性期反应物和内毒素活性。还将分析血清中的口腔微生物IgG抗体。将评估结局（PTB/LBW vs.正常新生儿）和组间（实验组vs.对照组）临床和实验室参数的差异。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.