Yoder Bradley A, Coalson Jacqueline J, Winter Vicki T, Siler-Khodr Teresa, Duffy Lynne B, Cassell Gail H
Department of Pathology, University of Texas Health Science Center, San Antonio, TX 78284, USA.
Pediatr Res. 2003 Dec;54(6):797-807. doi: 10.1203/01.PDR.0000091284.84322.16. Epub 2003 Aug 20.
Current nonhuman models for bronchopulmonary dysplasia have not included perinatal infection. We studied the effects of antenatal Ureaplasma urealyticum (Uu) infection in the 125-d immature baboon. Ten 125-d gestation (term = 185 d) baboon dams were delivered after intra-amniotic inoculation with Uu. Serial blood and tracheal aspirate samples were analyzed for Uu colony-forming units, IL-6, IL-8, and cell counts. Physiologic parameters were serially recorded. Lung histology was examined after 14 d of ventilation and compared with unexposed controls. All Uu-exposed animals had >4 x 102 CFU in tracheal aspirate at 24 h. Four of nine Uu animals remained heavily colonized [(+) Uu] at necropsy (>6 x 103). Five animals had negative or low tracheal colony-forming units. All Uu animals had significant increases for white blood cells, IL-6, and IL-8 in amniotic and fetal lung fluid. Compared with controls, (+) Uu animals had significantly higher fraction of inspired oxygen, airway pressures, oxygenation index, and ventilation efficiency index between 48 and 240 h and had significantly elevated tracheal IL-6 and IL-8 concentrations between 72 and 240 h. Compared with controls (-) Uu animals had significantly better oxygenation index and ventilation efficiency index scores between 48 and 144 h. Lung histopathology in both Uu groups showed more severe bronchiolitis and interstitial pneumonitis compared with controls. Two patterns of disease were observed after Uu perinatal infection. Persistent colonization manifested a picture consistent with acute pneumonitis, worse lung function from 2 to 10 d, and prolonged elevated tracheal cytokines. Colonized animals that subsequently cleared Uu from the lung demonstrated early improved lung function compared with unexposed controls yet still manifested mixed bronchiolitis and interstitial pneumonitis at necropsy. Inherent immune system responses may determine outcome of perinatal Ureaplasma colonization.
目前用于支气管肺发育不良的非人模型未纳入围产期感染因素。我们研究了产前解脲脲原体（Uu）感染对125日龄未成熟狒狒的影响。10只妊娠125日（足月为185日）的狒狒母猴在羊膜腔内接种Uu后分娩。对系列血液和气管吸出物样本进行Uu菌落形成单位、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）及细胞计数分析。连续记录生理参数。通气14天后检查肺组织学，并与未暴露的对照组进行比较。所有暴露于Uu的动物在24小时时气管吸出物中的菌落形成单位>4×10²CFU。9只Uu感染动物中有4只在尸检时仍有大量定植[（+）Uu]（>6×10³）。5只动物气管菌落形成单位为阴性或很低。所有Uu感染动物羊膜液和胎儿肺液中的白细胞、IL-6和IL-8均显著增加。与对照组相比，（+）Uu动物在48至240小时之间吸入氧分数、气道压力、氧合指数和通气效率指数显著更高，在72至240小时之间气管IL-6和IL-8浓度显著升高。与对照组相比，（-）Uu动物在48至144小时之间氧合指数和通气效率指数评分显著更好。与对照组相比，两个Uu组的肺组织病理学均显示细支气管炎和间质性肺炎更严重。Uu围产期感染后观察到两种疾病模式。持续定植表现为与急性肺炎一致的情况，在2至10天肺功能更差，气管细胞因子持续升高。随后从肺中清除Uu的定植动物与未暴露的对照组相比，肺功能早期有所改善，但在尸检时仍表现为混合性细支气管炎和间质性肺炎。固有免疫系统反应可能决定围产期解脲脲原体定植的结果。
