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静脉内游离和二肽结合型谷氨酰胺维持实验性内毒素血症的肠道微循环。

Intravenous free and dipeptide-bound glutamine maintains intestinal microcirculation in experimental endotoxemia.

机构信息

Department of Anesthesia, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.

出版信息

Nutrition. 2012 May;28(5):588-93. doi: 10.1016/j.nut.2011.09.021. Epub 2012 Jan 4.

Abstract

OBJECTIVE

The administration of glutamine (Gln), which is depleted in critical illness, is associated with an improvement of gut metabolism, structure, and function. The aim of the present study was to evaluate the effects of intravenous Gln and its galenic formulation, l-alanyl-l-glutamine dipeptide (AlaGln), on the intestinal microcirculation during experimental endotoxemia using intravital fluorescence microscopy. Gln or AlaGln administration was performed as pretreatment or post-treatment, respectively. To identify further the underlying mechanisms, amino acid levels were studied.

METHODS

Sixty male Lewis rats were randomly divided into six groups (n = 10/group): control, LPS (lipopolysaccharide 5 mg/kg intravenously), Gln/LPS (LPS animals pretreated with Gln 0.75 g/kg Gln intravenously), AlaGln/LPS (LPS animals pretreated with AlaGln intravenously, 0.75 g/kg Gln content), LPS/Gln (LPS animals post-treated with Gln 0.75 g/kg intravenously), and LPS/AlaGln (LPS animals post-treated with AlaGln intravenously, 0.75 g/kg Gln content). Two hours after the endotoxin challenge, the microcirculation of the terminal ileum was studied using intravital fluorescence microscopy. Blood samples were drawn at the beginning, during, and the end of the experiment to determine the amino acid levels.

RESULTS

The Gln and AlaGln pre- and post-treatment, respectively, prevented the LPS-induced decrease in the functional capillary density of the intestinal muscular and mucosal layers (P < 0.05). The number of adherent leukocytes in the submucosal venules was significantly attenuated after the Gln and AlaGln pre- and post-treatment (P < 0.05).

CONCLUSION

The Gln and AlaGln administrations improved the intestinal microcirculation by increasing the functional capillary density of the intestinal wall and decreasing the submucosal leukocyte activation.

摘要

目的

在危重病中消耗的谷氨酰胺(Gln)的给药与改善肠道代谢、结构和功能有关。本研究的目的是使用活体荧光显微镜评估静脉内 Gln 及其制剂 l-丙氨酰-l-谷氨酰胺二肽(AlaGln)在实验性内毒素血症期间对肠道微循环的影响。Gln 或 AlaGln 的给药分别作为预处理或后处理进行。为了进一步确定潜在的机制,研究了氨基酸水平。

方法

60 只雄性 Lewis 大鼠随机分为六组(n = 10/组):对照组、LPS(静脉内 5mg/kg 脂多糖)、Gln/LPS(静脉内预先给予 Gln 0.75g/kg 的 LPS 动物)、AlaGln/LPS(静脉内预先给予 AlaGln 的 LPS 动物,0.75g/kg Gln 含量)、LPS/Gln(静脉内给予 Gln 0.75g/kg 的 LPS 动物后处理)和 LPS/AlaGln(静脉内给予 AlaGln 0.75g/kg 的 LPS 动物后处理)。内毒素挑战后 2 小时,使用活体荧光显微镜研究末端回肠的微循环。在实验开始、期间和结束时抽取血液样本以确定氨基酸水平。

结果

Gln 和 AlaGln 的预处理和后处理分别预防了 LPS 诱导的肠道肌层和黏膜层功能毛细血管密度降低(P < 0.05)。Gln 和 AlaGln 的预处理和后处理后,黏膜下小静脉中的黏附白细胞数量明显减少(P < 0.05)。

结论

Gln 和 AlaGln 的给药通过增加肠壁的功能毛细血管密度和减少黏膜下白细胞激活来改善肠道微循环。

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