Department of Pharmacology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
Mol Biol Rep. 2022 Jul;49(7):5831-5842. doi: 10.1007/s11033-022-07358-5. Epub 2022 Mar 19.
Prenatal glucocorticoid (GC) is clinically administered to pregnant women who are at risk of preterm birth for the maturation of cardiopulmonary function. Preterm and low-birth-weight infants often experience liver dysfunction after birth because their livers are immature. However, the effects of prenatal GC administration on the liver remain unclear. We aimed to investigate the effects of prenatal GC administration on the maturation of liver hepatocytes in preterm rats.
Dexamethasone (DEX) was administered to pregnant Wistar rats on gestational days 17 and 19 before cesarean section. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the mRNA levels of albumin, hepatocyte nuclear factor-4 alpha (HNF4α), hepatocyte growth factor (HGF), thymus cell antigen 1 (Thy-1), cyclin B, and Cyclin-dependent kinase 1 (CDK1) in the liver samples. Immunohistochemical staining and enzyme-linked immunosorbent assay were performed to examine protein production. The hepatocytes enlarged because of growth and prenatal DEX administration. Albumin, HNF4α, and HGF levels increased secondary to growth and prenatal DEX administration. The levels of the cell cycle markers cyclin B and CDK1 gradually decreased during growth and with DEX administration.
The results suggest that prenatal GC administration leads to hepatocyte maturation via expression of HNF4α and HGF in preterm fetuses.
临床上，为了使心肺功能成熟，会对有早产风险的孕妇给予产前糖皮质激素（GC）。早产儿和低出生体重儿出生后常出现肝功能障碍，因为其肝脏不成熟。然而，产前 GC 给药对肝脏的影响尚不清楚。我们旨在研究产前 GC 给药对早产大鼠肝脏肝细胞成熟的影响。
在剖宫产前的妊娠第 17 天和第 19 天，对 Wistar 大鼠给予地塞米松（DEX）。通过实时逆转录-聚合酶链反应（RT-PCR）测定肝脏样本中白蛋白、肝细胞核因子-4α（HNF4α）、肝细胞生长因子（HGF）、胸腺细胞抗原 1（Thy-1）、细胞周期蛋白 B 和细胞周期蛋白依赖性激酶 1（CDK1）的 mRNA 水平。进行免疫组织化学染色和酶联免疫吸附试验以检测蛋白质产生。由于生长和产前 DEX 给药，肝细胞增大。白蛋白、HNF4α 和 HGF 水平因生长和产前 DEX 给药而升高。细胞周期标志物细胞周期蛋白 B 和 CDK1 的水平在生长过程中逐渐下降，并随 DEX 给药而下降。
这些结果表明，产前 GC 给药通过在早产胎儿中表达 HNF4α 和 HGF 导致肝细胞成熟。
