间歇性缺氧期间补充鱼油和/或抗氧化剂的新生大鼠生长和碳水化合物代谢的生物标志物

IF 1.6 4区 医学 Q4 CELL BIOLOGY
Despoina Myrsini Galetaki , Charles L. Cai , Kulsajan S. Bhatia , Vivian Chin , Jacob V. Aranda , Kay D. Beharry
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引用次数: 1

摘要

目的极低胎龄新生儿(ELGANs)在治疗性吸氧过程中经常出现间歇性缺氧(IH)。ELGAN产后生长发育不良,需要补充脂质。脂质是活性氧的靶标,导致脂质过氧化和细胞死亡,尤其是在抗氧化系统受损的早产儿中。我们检验了早期补充脂质和/或抗氧化剂促进暴露于IH的新生大鼠生长并影响碳水化合物代谢的生物标志物的假设。设计新生大鼠(n=18/组)在高氧(50%O2)或室内空气(RA)期间暴露于短暂缺氧(12%O2),从出生(P0)到P14,在此期间他们每天口服补充:1)鱼油;2) 橄榄油中的辅酶Q10;3) 谷胱甘肽纳米粒子;4) 鱼油+辅酶Q10;或5)橄榄油。在P21时,评估血浆样本中的葡萄糖、胰岛素、葡萄糖激酶(GCK)、胰高血糖素、胰高糖素样肽(GLP)-1、生长激素(GH)、皮质酮和胃饥饿素。评估肝脏的组织病理学、细胞凋亡(末端脱氧核苷酸转移酶dUTP缺口末端标记、TUNEL染色)、生长激素、胰岛素样生长因子(IGF)-I、生长激素结合蛋白(GHBP)和IGF结合蛋白(IGFBP)-3,用鱼油、nGSH和鱼油+CoQ10组合对其进行减毒。IH还降低了血糖、胰岛素、GCK和胃饥饿素,但增加了GLP-1。所有治疗均能改善IH患者的血糖,但仅CoQ10和nGSH组的胰岛素水平更高。辅酶Q10、鱼油和辅酶Q10+鱼油使胰高血糖素增加,而nGSH和辅酶Q11+鱼油使皮质酮增加。肝脏中IGF-I和IGFBP-3在IH中显著升高,而在RA和IH中,CoQ10和鱼油引起GH缺陷。nGSH和CoQ10+鱼油联合治疗降低了RA和IH中的IGF-I,但增加了IGFBP-3。结论新生儿IH会损害肝脏生长,并对肝细胞造成严重损伤。在IH的所有补充剂中,nGSH和鱼油+CoQ10组合对保持肝脏生长和碳水化合物代谢最有效。数据表明,这些补充剂可以改善出生后不良的器官和身体生长;以及与新生儿IH相关的代谢功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biomarkers of growth and carbohydrate metabolism in neonatal rats supplemented with fish oil and/or antioxidants during intermittent hypoxia

Objective

Extremely low gestational age neonates (ELGANs) experience frequent intermittent hypoxia (IH) episodes during therapeutic oxygen. ELGANs exhibit poor postnatal growth requiring lipid supplementation. Lipids are targets of reactive oxygen species resulting in lipid peroxidation and cell death, particularly in preterm infants with compromised antioxidant systems. We tested the hypothesis that early supplementation with lipids and/or antioxidants promotes growth and influences biomarkers of carbohydrate metabolism in neonatal rats exposed to IH.

Design

Newborn rats (n = 18/group) were exposed to brief hypoxia (12% O2) during hyperoxia (50% O2), or room air (RA), from birth (P0) to P14 during which they received daily oral supplementation with: 1) fish oil; 2) Coenzyme Q10 (CoQ10) in olive oil; 3) glutathione nanoparticles (nGSH); 4) fish oil+CoQ10; or 5) olive oil. At P21, plasma samples were assessed for glucose, insulin, glucokinase (GCK), glucagon, glucagon-like peptide (GLP)-1, growth hormone (GH), corticosterone, and ghrelin. Liver was assessed for histopathology, apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling, TUNEL stain), and GH, insulin-like growth factor (IGF)-I, GH binding protein (GHBP), and IGF binding protein (IGFBP)-3.

Results

Neonatal IH resulted in decreased liver weight and liver/body weight ratios, as well as hepatocyte swelling, steatosis, and apoptosis, which were attenuated with fish oil, nGSH, and combined fish oil+CoQ10. IH also decreased plasma glucose, insulin, GCK, and ghrelin, but increased GLP-1. All treatments improved plasma glucose in IH, but insulin was higher with CoQ10 and nGSH only. Glucagon was increased with CoQ10, fish oil, and CoQ10 + fish oil, while corticosterone was higher with nGSH and CoQ10 + fish oil. IGF-I and IGFBP-3 were significantly higher in the liver with CoQ10 in IH, while deficits in GH were noted with CoQ10 and fish oil in RA and IH. Treatment with nGSH and combined CoQ10 + fish oil reduced IGF-I in RA and IH but increased IGFBP-3.

Conclusions

Neonatal IH impairs liver growth with significant hepatocyte damage. Of all supplements in IH, nGSH and combined fish oil+CoQ10 were most effective for preserving liver growth and carbohydrate metabolism. Data suggest that these supplements may improve poor postnatal organ and body growth; and metabolic dysfunction associated with neonatal IH.

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来源期刊
Growth Hormone & Igf Research
Growth Hormone & Igf Research 医学-内分泌学与代谢
CiteScore
3.30
自引率
0.00%
发文量
38
审稿时长
57 days
期刊介绍: Growth Hormone & IGF Research is a forum for research on the regulation of growth and metabolism in humans, animals, tissues and cells. It publishes articles on all aspects of growth-promoting and growth-inhibiting hormones and factors, with particular emphasis on insulin-like growth factors (IGFs) and growth hormone. This reflects the increasing importance of growth hormone and IGFs in clinical medicine and in the treatment of diseases.
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