Rounioja Samuli, Räsänen Juha, Ojaniemi Marja, Glumoff Virpi, Autio-Harmainen Helena, Hallman Mikko
Department of Pediatrics and Biocenter Oulu, P.O. Box 5000, FIN-90014 University of Oulu, Finland.
Am J Pathol. 2005 Jun;166(6):1585-92. doi: 10.1016/S0002-9440(10)62469-8.
Intra-amniotic lipopolysaccharide (LPS) causes an acute inflammatory response and cardiac dysfunction in fetal mice. We hypothesized that the placenta protects the fetus against maternally administered bacterial toxins, delaying the onset of a fetal inflammatory response and vascular compromise. At 14 to 15 days of gestation, DBA mice were randomized to receive LPS (2.4 mg/kg) or vehicle intraperitoneally. Doppler ultrasonography of fetal cardiovascular hemodynamics was performed before and 6 hours after maternal LPS. Six hours after the LPS, maternal serum concentrations of tumor necrosis factor-alpha and interleukin (IL)-6 (P < 0.05) were increased. Placenta showed severe maternal vascular dilatation and congestion. The expressions of tumor necrosis factor-alpha, IL-1alpha, and IL-6 (P < 0.05) were increased, and the expression of Toll-like receptor 4 was constitutive in placenta. The expression of Toll-like receptor 2 increased (P < 0.05) and was detected in labyrinthine macrophages. No inflammatory activation was found in fetal tissues, and amniotic fluid revealed no significant increase in cytokines. The ultrasonographic examination demonstrated increased fetal cardiac afterload after LPS, with 65% of the fetuses exhibiting atrioventricular valve regurgitation. In conclusion, maternal inflammatory insult activates placental labyrinthine macrophages leading to an acute increase in placental vascular resistance and fetal cardiac dysfunction without an inflammatory response in fetus.
羊膜腔内注射脂多糖（LPS）可导致胎鼠出现急性炎症反应和心脏功能障碍。我们推测，胎盘可保护胎儿免受母体给予的细菌毒素影响，延缓胎儿炎症反应和血管损伤的发生。在妊娠14至15天时，将DBA小鼠随机分为两组，分别经腹腔注射LPS（2.4 mg/kg）或溶剂。在母体注射LPS前及注射后6小时，对胎儿心血管血流动力学进行多普勒超声检查。注射LPS后6小时，母体血清中肿瘤坏死因子-α和白细胞介素（IL）-6的浓度升高（P < 0.05）。胎盘显示母体血管严重扩张和充血。肿瘤坏死因子-α、IL-1α和IL-6的表达增加（P < 0.05），Toll样受体4在胎盘中呈组成性表达。Toll样受体2的表达增加（P < 0.05），并在迷路巨噬细胞中检测到。在胎儿组织中未发现炎症激活，羊水细胞因子也未显著增加。超声检查显示，注射LPS后胎儿心脏后负荷增加，65%的胎儿出现房室瓣反流。总之，母体炎症损伤激活胎盘迷路巨噬细胞，导致胎盘血管阻力急性增加和胎儿心脏功能障碍，而胎儿未出现炎症反应。
