PDF(Pubmed)
Abstract：
Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatonin analogue, on PNS-provoked IR in the periphery and the hippocampus in male and female offspring. Pregnant Sprague-Dawley rats were exposed to chronic stress (one short-term stressor on a daily basis and one long-term stressor on a nightly basis) from the first gestation week until birth. Vehicle or Pir 20 mg/kg were administered intraperitoneally for 21 days. Plasma glucose, serum insulin levels, and the homeostasis model assessment of insulin resistance (HOMA-IR) were determined as markers of peripheral IR. For the hippocampal IR assessment, insulin receptors (IRs) and glucose transporter 4 (GLUT4) were examined. Prenatally stressed offspring of both sexes indicated enhanced plasma glucose and serum insulin concentrations, increased HOMA-IR, and decreased hippocampal GLUT4 only in male rats. The PNS-induced changes were corrected by chronic treatment with Pir. The present results suggest that the melatoninergic compound Pir exerts beneficial effects on altered glucose/insulin homeostasis in PNS-exposed offspring.
摘要：
产前应激（PNS），这改变了后代的下丘脑-垂体-肾上腺轴功能，在以后的生活中易患胰岛素抵抗（IR），并与许多疾病有关，包括认知和记忆障碍。目前,我们的主要目标是评估慢性吡罗美汀（Pir）给药的效果，褪黑激素类似物，在雄性和雌性后代的外周和海马中PNS引起的IR。从第一个妊娠周到出生，怀孕的Sprague-Dawley大鼠暴露于慢性压力（每天一个短期压力源，每晚一个长期压力源）。腹膜内施用载体或Pir20mg/kg,持续21天。血浆葡萄糖，血清胰岛素水平，和胰岛素抵抗的稳态模型评估（HOMA-IR）被确定为外周IR的标志物。对于海马IR评估，检查胰岛素受体（IR）和葡萄糖转运蛋白4（GLUT4）。两性的前应激后代表明血浆葡萄糖和血清胰岛素浓度升高，增加HOMA-IR，仅在雄性大鼠中海马GLUT4降低。PNS诱导的变化通过Pir的慢性治疗得到纠正。本结果表明，褪黑激素能化合物Pir对PNS暴露后代的葡萄糖/胰岛素稳态改变具有有益作用。
