Department of Molecular Genetics and Pathology, Maastricht University, Maastricht 6200 MD, The Netherlands.
Pediatr Res. 2010 Dec;68(6):466-72. doi: 10.1203/PDR.0b013e3181f70eeb.
Chorioamnionitis frequently induces a fetal inflammatory response syndrome (FIRS), characterized by an elevation of proinflammatory mediators and systemic inflammation. Although there is increasing evidence that inflammation and lipid metabolism influence each other, the effects of chorioamnionitis-induced FIRS on fetal lipid homeostasis are currently not known. Accordingly, we hypothesize that chorioamnionitis induces an inflammatory response in the fetal liver, consequently leading to metabolic disturbances. Chorioamnionitis was induced by intra-amniotic injection of 10 mg endotoxin (control) for 2 d or 2 wk before delivery. Saline injections were given to controls. The effect of chorioamnionitis on hepatic inflammation and metabolic parameters was analyzed in ovine fetuses at the GA of 125 d (normal GA = 150 d). We found that 2 d after the endotoxin injections, inflammatory markers were significantly higher compared with controls. In addition, lipid and glucose metabolism were disturbed in response to endotoxin. Moreover, the antioxidant state capacity was reduced, and hepatic damage was apparent. Two weeks after the endotoxin injections, the fetal livers were still inflamed and had higher glucose concentrations in the blood. In addition, the levels of markers for hepatic damage (alanine aminotransferase and aspartate aminotransferase) were increased. In conclusion, chorioamnionitis induces liver inflammation leading to metabolic disturbances in the fetus.
绒毛膜羊膜炎常引起胎儿炎症反应综合征（FIRS），其特征是促炎介质和全身炎症升高。尽管越来越多的证据表明炎症和脂质代谢相互影响，但绒毛膜羊膜炎引起的 FIRS 对胎儿脂质稳态的影响目前尚不清楚。因此，我们假设绒毛膜羊膜炎会在胎儿肝脏中引起炎症反应，进而导致代谢紊乱。通过在分娩前 2 天或 2 周内向羊膜腔内注射 10mg 内毒素（对照）来诱导绒毛膜羊膜炎。对照组给予生理盐水注射。在 GA 为 125 天（正常 GA = 150 天）的绵羊胎儿中分析绒毛膜羊膜炎对肝脏炎症和代谢参数的影响。我们发现，内毒素注射 2 天后，炎症标志物与对照组相比显著升高。此外，脂质和葡萄糖代谢也因内毒素而紊乱。此外，抗氧化状态能力降低，肝损伤明显。内毒素注射 2 周后，胎儿肝脏仍有炎症，血液中葡萄糖浓度升高。此外，肝损伤标志物（丙氨酸氨基转移酶和天冬氨酸氨基转移酶）的水平也升高。总之，绒毛膜羊膜炎会引起肝脏炎症，导致胎儿代谢紊乱。
