AN EXPERIMENTAL MODEL FOR CHORIOAMNIONITIS AND PREMATURITY

绒毛膜羊膜炎和早产的实验模型

• 批准号: 7348889
• 负责人: MICHAEL G GRAVETT
• 金额: $ 7.68万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7348889
• 关键词: EXPERIMENTAL; MODEL; CHORIOAMNIONITIS; PREMATURITY

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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。早产及其后果仍然是产科最重要的问题。12%的早产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，而且有可能是可以预防的。本研究的长期目标是：a)阐明感染诱发早产的病理生理机制；B)建立宫内感染与早产之间的细胞和分子联系；c)检验感染情况下合理干预策略对早产的效果。我们相信，如果成功，这些研究将促进适当的人体介入试验的快速发展。我们在非人类灵长类动物中建立了第一个实验模型，使用长期插管怀孕的恒河猴（胎盘和分娩的激素控制与人类相似），通过在羊膜内接种已知浓度的特定微生物（B群链球菌）来建立宫内感染。实验性羊膜内感染后，促炎细胞因子、前列腺素和基质金属蛋白酶（MMPs）相继产生。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，通过全身和/或羊膜内非特异性免疫调节剂（白介素-10或地塞米松）或前列腺素合成酶抑制剂（吲哚美辛）和适当的抗生素治疗，可以抑制感染引起的早产，延长妊娠期。