EXPERIMENTAL MODEL FOR CHORIODECIDUAL INFECTION & PRETERM LABOR IN MACAQUES

脉络膜蜕膜感染的实验模型

• 批准号: 6277391
• 负责人: MICHAEL G GRAVETT
• 金额: $ 7.42万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277391
• 关键词: Mammalia; Primates; bacteria; clinical research; endocrine gland /system; immunology; infant mortality; infection; inflammation; low birth weight infant human; mother /infant health care; reproductive system; women's health

Intrauterine infection is an important cause of preterm birth. We have previously demonstrated that experimental intraamniotic infection in rhesus monkeys leads to sequential increases in amniotic fluid (AF) cytokines (TNF and IL-1b) and prostaglandins (PGE2 and PGF2a), followed by preterm labor and delivery. However, the role of choriodecidual infection in preterm labor is unclear. To characterize the pathophysiologic sequence of events following choriodecidual infection, we utilized chronically instrumented rhesus monkeys with timed gestations in which choriodecidual infection was established by inoculation of either a low inoculum (<102 cfu; n=2), moderate inoculum (103-104 cfu; n=4), or high inoculum (>105 cfu; n=3) of Group B streptococcus (GBS) bacteria into the choriodecidual space. Following inoculation, labor occurred in none of 2 low inoculum, 2 of 4 moderate inoculum, and in 2 of 3 high inoculum animals. In the 4 animals with infection-induced labor, increases in uterine contractility occurred 21 hours (14-30 hrs) after inoculation. Increases in uterine contractility were preceded by intraamniotic invasion by the GBS in 3 of 4 animals by an average of 12 hours (6-24 hrs). AF proinflammatory cytokine and prostaglandin concentrations did not rise above pre-inoculation levels among those 5 animals in which inoculation did not result in labor. In contrast, significant increases in AF cytokines and prostaglandins were observed in the 4 laboring animals after, but not before, intraamniotic invasion of GBS Median AF Concentrations (pg/ml) Event TNF IL-1b PGE2 PGF2a Pre-inoculation 50 <20 430 86 Onset Labor 900 110 5,550 316 Delivery 1,320 844 15,754 1,474 These results demonstrate that choriodecidual inoculation may ascend to the amniotic cavity and that following the establishment of intraamniotic infection, preterm labor ensues. In contrast, choriodecidual inoculation without concurrent intraamniotic infection did not lead to preterm labor.

宫内感染是早产的重要原因。 我们 先前已证明实验性羊膜内感染 恒河猴中的羊水（AF）连续增加 细胞因子（TNF 和 IL-1b）和前列腺素（PGE2 和 PGF2a）， 其次是早产和分娩。 然而，角色 早产中的绒毛膜蜕膜感染尚不清楚。 表征 绒毛膜蜕膜后事件的病理生理顺序 感染，我们利用长期仪器化的恒河猴 定时妊娠，其中绒毛膜蜕膜感染是通过 低接种量（<102 cfu；n=2）、中度接种 组的接种量（103-104 cfu；n=4），或高接种量（>105 cfu；n=3） B 型链球菌 (GBS) 细菌进入脉络膜蜕膜间隙。 接种后，2 次低剂量接种均未发生分娩，2 次接种 4只中度接种动物，以及3只高接种动物中的2只。 在 4 感染引起分娩的动物，子宫增大 接种后21小时（14-30小时）出现收缩。 子宫收缩力增加之前是羊膜腔内收缩 4 只动物中的 3 只平均 12 小时（6-24 小时）。 AF 促炎细胞因子和前列腺素浓度 这 5 只动物中的病毒浓度没有上升到超过接种前的水平。 接种后并未导致分娩。 相比之下，显着 4 组中观察到 AF 细胞因子和前列腺素增加 GBS 羊膜内侵入之后而非之前的产程动物 中位 AF 浓度 (pg/ml) 事件 TNF IL-1b PGE2 PGF2a 预接种 50 <20 430 86 分娩开始 900 110 5,550 316 交付 1,320 844 15,754 1,474 这些结果表明 绒毛膜蜕膜接种可能上升至羊膜腔，并且 羊膜内感染建立后，早产 随后发生。 相反，没有同时进行绒毛膜蜕膜接种 羊膜腔内感染并未导致早产。