Besnier E, Clavier T, Tonon M C, Pelletier G, Dureuil B, Castel H, Compère V
Normandie Univ, UNIROUEN, INSERM U1239, DC2N, 76000, Rouen, France.
Institute for Research and Innovation in Biomedicine (IRIB), 76000, Rouen, France.
BMC Anesthesiol. 2018 Jul 27;18(1):96. doi: 10.1186/s12871-018-0557-x.
Several hypnotic drugs have been previously identified as modulators of food intake, but exact mechanisms remain unknown. Feeding behavior implicates several neuronal populations in the hypothalamic arcuate nucleus including orexigenic neuropeptide Y and anorexigenic pro-opiomelanocortin producing neurons. The aim of this study was to investigate in mice the impact of different hypnotic drugs on food consumption and neuropeptide Y or pro-opiomelanocortine mRNA expression level in the hypothalamic arcuate nucleus.
Saline control, isoflurane, thiopental, midazolam or propofol were administered to C57Bl/6 mice. Feeding behavior was evaluated during 6 h. In situ hybridization of neuropeptide Y and pro-opiomelanocortine mRNAs in the hypothalamus brain region was also performed. Data were analyzed by Kruskal Wallis test and analysis of variance (p < 0.05).
Midazolam, thiopental and propofol induced feeding behavior. Midazolam and thiopental increased neuropeptide Y mRNA level (respectively by 106 and 125%, p < 0.001) compared with control. Propofol and midazolam decreased pro-opiomelanocortine mRNA level by 31% (p < 0,01) compared with control. Isoflurane increased pro-opiomelanocortine mRNA level by 40% compared with control.
In our murine model, most hypnotics induced food consumption. The hypnotic-induced regulation of neuropeptide Y and pro-opiomelanocortine hypothalamic peptides is associated with this finding. Our data suggest that administration of some hypnotic drugs may affect hypothalamic peptide precursor and neuropeptide expression and concomittantly modulate food intake. Thus, this questions the choice of anesthetics for better care management of patients undergoing major surgery or at risk of undernutrition.
先前已确定几种催眠药物为食物摄入的调节剂，但确切机制仍不清楚。进食行为涉及下丘脑弓状核中的几个神经元群体，包括促食欲的神经肽Y和产生促黑素细胞激素原的厌食神经元。本研究的目的是在小鼠中研究不同催眠药物对食物消耗以及下丘脑弓状核中神经肽Y或促黑素细胞激素原mRNA表达水平的影响。
对C57Bl/6小鼠给予生理盐水对照、异氟烷、硫喷妥钠、咪达唑仑或丙泊酚。在6小时内评估进食行为。还对下丘脑脑区的神经肽Y和促黑素细胞激素原mRNA进行了原位杂交。数据通过Kruskal Wallis检验和方差分析进行分析（p < 0.05）。
咪达唑仑、硫喷妥钠和丙泊酚诱导进食行为。与对照组相比，咪达唑仑和硫喷妥钠使神经肽Y mRNA水平分别增加了106%和125%（p < 0.001）。与对照组相比，丙泊酚和咪达唑仑使促黑素细胞激素原mRNA水平降低了31%（p < 0.01）。与对照组相比，异氟烷使促黑素细胞激素原mRNA水平增加了40%。
在我们的小鼠模型中，大多数催眠药会诱导食物消耗。催眠药诱导的下丘脑神经肽Y和促黑素细胞激素原调节与这一发现相关。我们的数据表明，某些催眠药物的给药可能会影响下丘脑肽前体和神经肽表达，并随之调节食物摄入。因此，这对为接受大手术或有营养不良风险的患者选择更好的护理管理麻醉剂提出了质疑。
