Rinaldi Sara F, Makieva Sofia, Frew Lorraine, Wade Jean, Thomson Adrian J W, Moran Carmel M, Norman Jane E, Stock Sarah J
Tommy's Centre for Maternal and Fetal Health at the Medical Research Council Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
Am J Pathol. 2015 May;185(5):1201-6. doi: 10.1016/j.ajpath.2015.01.009. Epub 2015 Mar 6.
Mouse models are used to study mechanisms that link intrauterine infection and preterm birth (PTB). To mimic intrauterine infection, lipopolysaccharide (LPS) is commonly injected into the uterus via minilaparotomy, which is invasive, and can cause PTB in control animals. We hypothesized that less-invasive ultrasound-guided intrauterine LPS injection or intravaginal LPS administration could induce PTB by stimulating an inflammatory response of the uteroplacental tissues, while minimizing PTB in control animals. On day 17 of gestation mice received LPS intravaginally (10 to 240 μg; n = 3 to 8) or into the uterus (20 μg) under ultrasound guidance (n = 7) or via laparotomy (n = 7). Control animals received phosphate-buffered saline (PBS; n = 5 to 7). Intrauterine administration of LPS, both under ultrasound guidance and via laparotomy, induced delivery earlier than in PBS control groups (P < 0.01). Intravaginal LPS administration did not stimulate PTB. Quantitative real-time PCR and immunohistochemistry of tissues harvested 6 hours after treatment confirmed that ultrasound-guided LPS administration induced a localized inflammatory response. Ultrasound-guided intrauterine LPS injection reliably induces PTB in the mouse and mimics the local inflammatory and immune responses observed in the more-invasive laparotomy model of inflammation-induced PTB. Ultrasound-guided intrauterine LPS injection is a useful novel model of PTB for future studies and concords with the principles of reduction, replacement, and refinement.
小鼠模型用于研究与宫内感染和早产（PTB）相关的机制。为模拟宫内感染，通常通过小型剖腹术将脂多糖（LPS）注入子宫，这种方法具有侵入性，且可在对照动物中导致早产。我们推测，侵入性较小的超声引导下宫内LPS注射或经阴道给予LPS可通过刺激子宫胎盘组织的炎症反应诱导早产，同时使对照动物的早产发生率降至最低。在妊娠第17天，小鼠经阴道接受LPS（10至240μg；n = 3至8），或在超声引导下（n = 7）或通过剖腹术（n = 7）将LPS注入子宫（20μg）。对照动物接受磷酸盐缓冲盐水（PBS；n = 5至7）。超声引导下和通过剖腹术进行的宫内LPS给药均比PBS对照组更早诱导分娩（P < 0.01）。经阴道给予LPS未刺激早产。治疗6小时后采集的组织进行定量实时PCR和免疫组织化学检测证实，超声引导下给予LPS可诱导局部炎症反应。超声引导下宫内LPS注射可可靠地在小鼠中诱导早产，并模拟在炎症诱导早产的侵入性更强的剖腹术模型中观察到的局部炎症和免疫反应。超声引导下宫内LPS注射是一种用于未来研究的有用的新型早产模型，符合减少、替代和优化原则。
