Yeh Chiu-Li, Hsu Chun-Sen, Yeh Sung-Ling, Lin Ming-Tsan, Chen Wei-Jao
Graduate Institute of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Nutrition. 2006 Apr;22(4):408-13. doi: 10.1016/j.nut.2005.10.007. Epub 2006 Feb 3.
This study investigated the effects of glutamine (Gln) on plasma intracellular adhesion molecule-1 levels and leukocyte integrin (CD11a/CD18 and CD11b/CD18) expressions in gut-derived sepsis. Myeloperoxidase (MPO) activities in organs were also analyzed to identify the extent of tissue injury resulting from neutrophil infiltration.
Mice were randomly assigned to a normal group (NC), a control group, or a Gln group. The NC group was fed standard chow diet; the control group was fed a common semipurified diet; and the Gln group received a diet in which part of the casein was replaced by Gln, which provided 25% of total amino acid nitrogen. After 3 wk, sepsis was induced by cecal ligation and puncture (CLP) in the control and Gln groups. Mice in the experimental groups were killed at 0, 6, 12, and 24 h after CLP. Mice in the NC group were killed when CLP was performed. Blood and organ samples were collected for further analysis.
Plasma intracellular adhesion molecule-1 levels were significantly lower in the Gln group than in the control group at 6, 12, and 24 h after CLP. Expressions of lymphocyte CD11a/CD18 were significantly higher, whereas polymorphonuclear lymphocyte expressions of CD11b/CD18 were lower in the Gln group than in the corresponding control group at 6 and 12 h after CLP. In comparisons of MPO activities in various organs, the Gln group had lower MPO activities at 6 and 12 h in the lung, at 6, 12, and 24 h in the liver, at 12 and 24 h in the kidneys, and at 12 h in the intestine than those in the control group.
Results of this study demonstrate that a Gln-supplemented enteral diet increased lymphocyte CD11a/CD18 expressions, whereas neutrophil CD11b/CD18 expressions, circulating intracellular adhesion molecule-1 levels, and MPO activities in various organs decreased with gut-derived sepsis. These findings suggest that, under septic conditions, Gln administration may enhance lymphocyte function, attenuate interactions between polymorphonuclear lymphocytes and endothelium, and thus may decrease neutrophil infiltration into tissues.
本研究调查了谷氨酰胺(Gln)对肠道源性脓毒症时血浆细胞间黏附分子-1水平及白细胞整合素(CD11a/CD18和CD11b/CD18)表达的影响。还分析了各器官中的髓过氧化物酶(MPO)活性,以确定中性粒细胞浸润所致组织损伤的程度。
将小鼠随机分为正常组(NC)、对照组或Gln组。NC组给予标准饲料;对照组给予普通半纯化饲料;Gln组给予用Gln替代部分酪蛋白的饲料,Gln提供总氨基酸氮的25%。3周后,对照组和Gln组通过盲肠结扎和穿刺(CLP)诱导脓毒症。实验组小鼠在CLP后0、6、12和24小时处死。NC组小鼠在进行CLP时处死。采集血液和器官样本进行进一步分析。
CLP后6、12和24小时,Gln组血浆细胞间黏附分子-1水平显著低于对照组。CLP后6和12小时,Gln组淋巴细胞CD11a/CD18表达显著升高,而多形核淋巴细胞CD11b/CD18表达低于相应对照组。在比较各器官的MPO活性时,Gln组在肺脏6和12小时、肝脏6、12和24小时、肾脏12和24小时以及肠道12小时的MPO活性低于对照组。
本研究结果表明,补充Gln的肠内饮食可增加淋巴细胞CD11a/CD18表达,而肠道源性脓毒症时中性粒细胞CD11b/CD18表达、循环细胞间黏附分子-1水平及各器官MPO活性降低。这些发现提示,在脓毒症条件下,给予Gln可能增强淋巴细胞功能,减弱多形核淋巴细胞与内皮细胞之间的相互作用,从而可能减少中性粒细胞向组织的浸润。