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新生儿口腔蔗糖处理对成年后生长和肝脏胆碱及糖皮质激素代谢的性别特异性影响。

Sex-specific effects of neonatal oral sucrose treatment on growth and liver choline and glucocorticoid metabolism in adulthood.

机构信息

Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada.

BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2021 Nov 1;321(5):R802-R811. doi: 10.1152/ajpregu.00091.2021. Epub 2021 Oct 6.

Abstract

Hospitalized preterm infants experience painful medical procedures. Oral sucrose is the nonpharmacological standard of care for minor procedural pain relief. Infants are treated with numerous doses of sucrose, raising concerns about potential long-term effects. The objective of this study was to determine the long-term effects of neonatal oral sucrose treatment on growth and liver metabolism in a mouse model. Neonatal female and male mice were randomly assigned to one of two oral treatments ( = 7-10 mice/group/sex): sterile water or sucrose. Pups were treated 10 times/day for the first 6 days of life with 0.2 mg/g body wt of respective treatments (24% solution; 1-4 μL/dose) to mimic what is given to preterm infants. Mice were weaned at age 3 wk onto a control diet and fed until age 16 wk. Sucrose-treated female and male mice gained less weight during the treatment period and were smaller at weaning than water-treated mice ( ≤ 0.05); no effect of sucrose treatment on body weight was observed at adulthood. However, adult sucrose-treated female mice had smaller tibias and lower serum insulin-like growth factor-1 than adult water-treated female mice ( ≤ 0.05); these effects were not observed in males. Lower liver -adenosylmethionine, phosphocholine, and glycerophosphocholine were observed in adult sucrose-treated compared with water-treated female and male mice ( ≤ 0.05). Sucrose-treated female, but not male, mice had lower liver free choline and higher liver betaine compared with water-treated female mice ( < 0.01). Our findings suggest that repeated neonatal sucrose treatment has long-term sex-specific effects on growth and liver methionine and choline metabolism.

摘要

住院早产儿会经历痛苦的医疗程序。口服蔗糖是缓解轻微程序疼痛的非药物标准护理。婴儿接受多次蔗糖治疗,引起了对潜在长期影响的关注。本研究的目的是确定新生儿口服蔗糖处理对小鼠模型中生长和肝脏代谢的长期影响。新生雌性和雄性小鼠被随机分为两种口服处理组(每组/性别有 7-10 只小鼠):无菌水或蔗糖。在生命的头 6 天,每天对幼鼠进行 10 次治疗,给予 0.2mg/g 体重的相应处理(24%溶液;1-4 μL/剂量),以模拟给予早产儿的剂量。幼鼠在 3 周龄时断奶并接受对照饮食喂养,直至 16 周龄。与水治疗的小鼠相比,蔗糖治疗的雌性和雄性小鼠在治疗期间体重增加较少,断奶时体型较小( ≤ 0.05);在成年期未观察到蔗糖处理对体重的影响。然而,成年蔗糖处理的雌性小鼠的胫骨较小,血清胰岛素样生长因子-1 水平低于成年水治疗的雌性小鼠( ≤ 0.05);这些影响在雄性小鼠中未观察到。与水治疗的雌性和雄性小鼠相比,成年蔗糖处理的雌性和雄性小鼠的肝脏 -腺苷甲硫氨酸、磷酸胆碱和甘油磷酸胆碱较低( ≤ 0.05)。与水治疗的雌性小鼠相比,蔗糖处理的雌性,但不是雄性,小鼠的肝脏游离胆碱较低,甜菜碱较高( < 0.01)。我们的研究结果表明,反复的新生儿蔗糖处理对生长和肝脏蛋氨酸和胆碱代谢具有长期的性别特异性影响。

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