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孕期补充膳食肌酸:关于补充肌酸对刺毛鼠肌酸稳态和肾脏排泄功能影响的研究

Dietary creatine supplementation during pregnancy: a study on the effects of creatine supplementation on creatine homeostasis and renal excretory function in spiny mice.

作者信息

Ellery Stacey J, LaRosa Domenic A, Kett Michelle M, Della Gatta Paul A, Snow Rod J, Walker David W, Dickinson Hayley

机构信息

The Ritchie Centre, Hudson Institute of Medical Research, 27-31 Wright St, Clayton, Melbourne, 3168, Australia.

Department of Obstetrics and Gynecology, Monash University, Monash Medical Centre, Clayton, Melbourne, Australia.

出版信息

Amino Acids. 2016 Aug;48(8):1819-30. doi: 10.1007/s00726-015-2150-7. Epub 2015 Dec 22.

Abstract

Recent evidence obtained from a rodent model of birth asphyxia shows that supplementation of the maternal diet with creatine during pregnancy protects the neonate from multi-organ damage. However, the effect of increasing creatine intake on creatine homeostasis and biosynthesis in females, particularly during pregnancy, is unknown. This study assessed the impact of creatine supplementation on creatine homeostasis, body composition, capacity for de novo creatine synthesis and renal excretory function in non-pregnant and pregnant spiny mice. Mid-gestation pregnant and virgin spiny mice were fed normal chow or chow supplemented with 5 % w/w creatine for 18 days. Weight gain, urinary creatine and electrolyte excretion were assessed during supplementation. At post mortem, body composition was assessed by Dual-energy X-ray absorptiometry, or tissues were collected to assess creatine content and mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) and the creatine transporter (CrT1). Protein expression of AGAT and GAMT was also assessed by Western blot. Key findings of this study include no changes in body weight or composition with creatine supplementation; increased urinary creatine excretion in supplemented spiny mice, with increased sodium (P < 0.001) and chloride (P < 0.05) excretion in pregnant dams after 3 days of supplementation; lowered renal AGAT mRNA (P < 0.001) and protein (P < 0.001) expressions, and lowered CrT1 mRNA expression in the kidney (P < 0.01) and brain (P < 0.001). Creatine supplementation had minimal impact on creatine homeostasis in either non-pregnant or pregnant spiny mice. Increasing maternal dietary creatine consumption could be a useful treatment for birth asphyxia.

摘要

最近从出生窒息的啮齿动物模型中获得的证据表明,孕期在母体饮食中补充肌酸可保护新生儿免受多器官损伤。然而,增加肌酸摄入量对雌性动物,尤其是孕期雌性动物的肌酸稳态和生物合成的影响尚不清楚。本研究评估了补充肌酸对未怀孕和怀孕的刺毛鼠的肌酸稳态、身体组成、肌酸从头合成能力和肾脏排泄功能的影响。妊娠中期的怀孕和未怀孕刺毛鼠被喂食普通饲料或添加5%(重量/重量)肌酸的饲料,持续18天。在补充期间评估体重增加、尿肌酸和电解质排泄情况。在剖检时,通过双能X线吸收法评估身体组成,或收集组织以评估肌酸含量以及肌酸合成酶精氨酸:甘氨酸脒基转移酶(AGAT)和胍乙酸甲基转移酶(GAMT)以及肌酸转运体(CrT1)的mRNA表达。还通过蛋白质印迹法评估AGAT和GAMT的蛋白质表达。本研究的主要发现包括:补充肌酸后体重和身体组成无变化;补充肌酸的刺毛鼠尿肌酸排泄增加,补充3天后怀孕母鼠的钠(P<0.001)和氯(P<0.05)排泄增加;肾脏AGAT的mRNA(P<0.001)和蛋白质(P<0.001)表达降低,肾脏(P<0.01)和大脑(P<0.001)中CrT1的mRNA表达降低。补充肌酸对未怀孕或怀孕的刺毛鼠的肌酸稳态影响极小。增加母体饮食中的肌酸摄入量可能是治疗出生窒息的一种有效方法。

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