EXPERIMENTAL MODEL FOR CHORIOAMNIONITIS AND PREMATURITY

早产是新生儿发病率和死亡率的主要原因。 在美国。8%的早产儿占到了 70%的围产儿死亡可归因于先天性畸形。 越来越多的证据表明，宫内感染是 这是导致早产的一个重要且有可能治愈的原因。然而， 感染导致早产的机制仍然存在 推测性和治疗策略未经测试，主要是因为人类 不能在感染后进行纵向研究。我们建议使用 妊娠恒河猴(n：36)120-130岁 妊娠天数，实验性宫内感染，与以前一样 描述(Gravett等人，Am J Obstet&Gynecol；171：1660-1667,1994) 为了研究感染之间的时间和数量关系， 细胞因子，前列腺素，脂肪氧合酶衍生物，类固醇激素， 细胞因子拮抗剂，以开发有效的早产 干预性策略。在术后稳定下来的一个 系绳，我们将(1)将促炎细胞因子IL-1β注入 羊膜腔通过预先放置的留置导管在 无感染(n=16)；(2)接种第8组链球菌(GBS) 进入羊水以确定宫内感染和早产 分娩组20例。将持续监测子宫收缩能力，并 羊水、母血和胎儿血液的定期样本(1-4 Cc)将用于二十烷类化合物、类固醇激素、 细胞因子、补体和热休克蛋白，以及对微生物 学习。在没有感染的情况下注射IL-1β之前， 促炎细胞因子产生的有效抑制物 (地塞米松、白介素10)或前列腺素的产生 (消炎痛)将用于确定最有效的 干预下调细胞因子/前列腺素级联反应和 相关的子宫活动。免疫抑制剂或前列腺素 合成酶抑制剂将以类似的方式与 抗生素在实验性宫内感染中的应用 GBS。蜕膜、胎盘和胎儿组织的样本将 在剖腹产手术中获得的微生物、组织病理学和 细胞因子信使核糖核酸定位和定量研究。胎儿是 初步可行并将被实施安乐死。产后，母亲会 用适当的抗生素治疗，以消除GBS 生殖道，并返回蜂群。这些研究将澄清 感染相关性早产与遗嘱的病理生理学 建议有效的干预策略。

Prematurity is the leading cause of neonatal morbidity and mortality in the United States. The 8% of neonates born prematurely account for 70% of all perinatal deaths hot attributed to congenital malformations. A growing body of evidence suggests that intrauterine infections are an important, and potentially treatable cause of prematurity. However, the mechanisms by which infection leads to prematurity remain speculative and treatment strategies untested largely because humans cannot be longitudinally studied following infection. We propose to use chronically instrumented pregnant rhesus monkeys (n: 36) at 120-130 days gestation with experimental intrauterine infection, as previously described (Gravett et al, Am J Obstet & Gynecol; 171:1660-1667,1994) to study the temporal and quantitative relationships among infection, cytokines, prostaglandins, lipoxygenase derivatives, steroid hormones, cytokine antagonists, and preterm labor in order to develop effective interventional strategies. After postoperative stabilization in a tether, we will (1) infuse proinflammatory cytokine IL-1beta into the amniotic cavity through previously placed indwelling catheters in the absence of infection (n=16); (2) inoculate Group 8 streptococci (GBS) into the amniotic fluid to establish intrauterine infection and preterm labor (n=20). Uterine contractility will be continuously monitored and periodic samples of amniotic fluid and maternal and fetal blood (1-4 cc) will be obtained for assays of eicosanoids, steroid hormones, cytokines, complement and heat-shock proteins, and for microbial studies. Prior to infusion of IL-1beta in the absence of infection, potent inhibitors of proinflammatory cytokine production (dexamethasone, interleukin-10) or prostaglandin production (indomethacin) will be used to ascertain the most effective intervention to down-regulate the cytokine/prostaglandin cascade and associated uterine activity. The immunosuppressants or prostaglandin synthase inhibitor will be similarly studied in combination with antibiotics in the setting of experimental intrauterine infection with GBS. Samples of the decidua, placenta, and fetal tissue will be obtained at cesarean section for microbiologic, histopathologic, and studies for cytokine mRNA localization and quantitation. The fetus is pre-viable and will be euthanized. Postpartum, the mother will be treated with appropriate antibiotics to eradicate the GBS from the genital tract and returned to the colony. These studies will clarify the pathophysiology of infection-associated preterm labor and will suggest effective interventional strategies.