Laboratoire de Biologie de la Nutrition, Faculté de Pharmacie, Université Paris-Descartes, Paris, France; Département de Gastroentérologie et Nutrition, Hôpital L'Archet, Nice, France.
Université Grenoble Alpes, Laboratoire Bioénergétique Fondamental et Appliqué, Grenoble, France; Département de Pédiatrie, Hôpital Couple Enfant, CHU Grenoble Alpes, Grenoble, France.
Nutrition. 2021 May;85:111118. doi: 10.1016/j.nut.2020.111118. Epub 2021 Feb 2.
Supplementing diet with citrulline has proved an efficient means of preserving nitrogen balance and improving nutritional status after massive intestinal resection. The aim of this study was to model the action of citrulline in gut-resected rats using a dose-ranging study focused on skeletal muscle nitrogen homeostasis.
Forty-six rats were randomly assigned to one of the following groups: citrulline 0.5 g·kg·d (n = 9), citrulline 1 g·kg·d (n = 7), citrulline 2.5 g·kg·d (n = 8), citrulline 5 g·kg·d (n = 8), control (n = 6), and sham (n = 8). The sham group underwent transection and the other groups underwent resection of 80% of the small intestine. All rats were then fed enteral nutrition (EN; all diets were isocaloric and isonitrogenous). After 10 d, the rats were sacrificed to measure and analyze animal weight; duodenum, jejunum, and ileum weight; and muscle trophicity. Protein fractional synthesis rate (FSR) and mammalian target of rapamycin complex (mTORC)1 activation were measured in the tibialis muscle.
There was a significant dose-dependent association between rat weight and citrulline dose up to 2.5 g·kg·d (P = 0.004). There was a significant improvement in tibialis weight correlated to plasma citrulline. Net protein FSR in the tibialis tended to be greater after resection and tended to return to baseline after citrulline supplementation. Citrulline supplementation significantly decreased the activated phosphorylated forms of S6 K1 (P = 0.003) and S6 RP (P = 0.003), with a significant positive association between myofibrillar FSR and activation of S6 K1 (r = 0.614; P = 0.02) and S6 RP (r = 0.601; P = 0.023). Jejunum weight was significantly positively correlated with plasma citrulline (r = 0.319; P = 0.0345).
Citrulline promotes body weight gain, preserves muscle trophicity, and enhances intestinal adaptation in a dose-dependent manner in a model of resected rats.
在进行大规模肠道切除后，通过补充瓜氨酸，已被证明是维持氮平衡和改善营养状况的有效手段。本研究旨在通过一项以骨骼肌氮平衡为重点的剂量范围研究，对肠道切除大鼠的瓜氨酸作用进行建模。
46 只大鼠被随机分为以下几组：瓜氨酸 0.5 g·kg·d（n=9）、瓜氨酸 1 g·kg·d（n=7）、瓜氨酸 2.5 g·kg·d（n=8）、瓜氨酸 5 g·kg·d（n=8）、对照组（n=6）和假手术组（n=8）。假手术组进行横断，其他组进行 80%小肠切除术。所有大鼠均接受肠内营养（EN；所有饮食均具有相同的热量和氮含量）。10 天后，处死大鼠以测量和分析动物体重、十二指肠、空肠和回肠重量以及肌肉营养状况。在比目鱼肌中测量蛋白的分数合成率（FSR）和雷帕霉素靶蛋白复合物（mTORC）1 的激活情况。
大鼠体重与瓜氨酸剂量之间存在显著的剂量依赖性关系，直至 2.5 g·kg·d（P=0.004）。胫骨重量的显著改善与血浆瓜氨酸相关。胫骨的净蛋白 FSR 在手术后趋于增加，并在瓜氨酸补充后趋于恢复到基线。瓜氨酸补充显著降低了 S6 K1 的磷酸化激活形式（P=0.003）和 S6 RP（P=0.003），肌原纤维 FSR 与 S6 K1 的激活呈显著正相关（r=0.614；P=0.02）和 S6 RP（r=0.601；P=0.023）。空肠重量与血浆瓜氨酸呈显著正相关（r=0.319；P=0.0345）。
瓜氨酸以剂量依赖的方式促进体重增加，维持肌肉营养，并增强切除大鼠模型中的肠道适应性。
