AN EXPERIMENTAL MODEL FOR CHORIOAMNIONITIS AND PREMATURITY

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。早产及其后果仍然是产科最重要的问题。12%的早产新生儿占非先天性畸形新生儿死亡的80%。宫内感染是早产的一个重要原因，也是可以预防的。本研究的长期目标是：a）阐明感染性早产的病理生理机制; B）建立宫内感染和早产之间的细胞和分子联系; c）测试感染背景下早产的合理干预策略的有效性。我们相信，如果成功，这些研究将促进适当的人类干预试验的快速发展。我们已经开发了第一个实验模型，在非人类灵长类动物使用长期插管妊娠恒河猴（胎盘和分娩的激素控制类似于人类），其中宫内感染是建立羊膜内接种已知浓度的特定微生物（B组链球菌）。在实验性羊膜内感染后，会相继产生促炎细胞因子、胰高血糖素和基质金属蛋白酶（MMPs）。然后，在所有情况下，子宫收缩，分娩和分娩，通常在72小时内。最近，我们证明，感染引起的早产可以抑制，并延长妊娠，全身和/或羊膜腔内治疗与非特异性免疫调节剂（白细胞介素-10或地塞米松）或前列腺素合成酶抑制剂（吲哚美辛）和适当的抗生素。

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. Prematurity, and its consequences, remain the most important problem in obstetrics. The 12% of neonates born prematurely account for 80% of neonatal deaths not attributable to congenital malformations. Intrauterine infections are an important, and potentially preventable, cause of preterm delivery. The long-term objectives of this research are: a) to elucidate the pathophysiologic mechanisms of infection-induced preterm labor; b) to establish the cellular and molecular links among intrauterine infection and preterm labor; and c) to test the efficacy of rational interventional strategies for preterm labor in the setting of infection. It is our belief that if successful, these studies will facilitate the rapid development of appropriate human interventional trials. We have developed the first experimental model in a nonhuman primate using chronically catheterized pregnant rhesus monkeys (both placentation and the hormonal control of parturition are similar to humans) in which intrauterine infection is established by the intraamniotic inoculation of known concentrations of a specific microorganism (Group B Streptococcus). Following experimental intraamniotic infection, there is sequential production of the proinflammatory cytokines, prostaglandins, and matrix metalloproteinases (MMPs). This is then followed in all cases by uterine contraction, labor and delivery, usually within 72 hours. Recently, we demonstrated that infection-induced preterm labor can be inhibited, and gestation prolonged, by systemic and/or intraamniotic treatment with non-specific immunomodulators (interleukin-10 or dexamethasone) or prostaglandin syntase inhibitors (indomethacin) and appropriate antibiotics.