Johnston Andrea N, Batts Tifini L, Langohr Ingeborg M, Moeller Cambri, Liu Chin-Chi, Sones Jennifer L
Departments of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
Biology (Basel). 2021 Nov 14;10(11):1179. doi: 10.3390/biology10111179.
Preeclampsia (PE) is a multisystemic disease of pregnancy affecting 2-8% of women worldwide. PE-induced liver disease is a rare but important complication of pregnancy. The pathogenesis of liver dysfunction in PE is poorly understood, but is correlated with dysregulated angiogenic, inflammatory, and hypoxic events in the early phase of placental development. Because BPH/5 mice develop the maternal and fetal hallmarks of PE during pregnancy, we hypothesized that they may also share the clinicopathologic findings of the human PE-associated hemolysis elevated liver transaminases low platelets (HELLP) syndrome. Using this model, we determined that microangiopathic hemolysis, thrombocytopenia, and elevated liver enzymes do not occur in mid to late gestation. Pregnant BPH/5 mice do not develop histologic evidence of hepatic inflammation, but they do have increased microsteatosis scores at preconception and in mid to late gestation that progress to macrosteatosis in a subset of mice in late gestation. The transcriptional upregulation of TNF-α, CXCL-10, and TLR-2 occurs in mid gestation prior to the onset of macrosteatosis. The BPH/5 female mouse is not a model of HELLP syndrome, but may be a model of fatty liver disease associated with pregnancy.
子痫前期(PE)是一种影响全球2%-8%孕妇的妊娠多系统疾病。PE所致的肝脏疾病是一种罕见但重要的妊娠并发症。PE中肝功能障碍的发病机制尚不清楚,但与胎盘发育早期血管生成、炎症和缺氧事件失调有关。由于BPH/5小鼠在孕期会出现PE的母体和胎儿特征,我们推测它们可能也具有人类PE相关的溶血、肝转氨酶升高、血小板减少(HELLP)综合征的临床病理表现。利用该模型,我们确定在妊娠中后期不会出现微血管病性溶血、血小板减少和肝酶升高。怀孕的BPH/5小鼠没有出现肝脏炎症的组织学证据,但在孕前以及妊娠中后期,它们的微脂肪变性评分增加,在妊娠后期一部分小鼠中进展为大脂肪变性。TNF-α、CXCL-10和TLR-2的转录上调发生在大脂肪变性出现之前的妊娠中期。BPH/5雌性小鼠不是HELLP综合征的模型,但可能是与妊娠相关的脂肪肝疾病的模型。