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丙氨酰-谷氨酰胺二肽对葡聚糖硫酸钠诱导结肠炎恢复期结肠炎症介质表达的影响。

Effects of alanyl-glutamine dipeptide on the expression of colon-inflammatory mediators during the recovery phase of colitis induced by dextran sulfate sodium.

机构信息

School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu Hsin Street, Taipei, 110, Taiwan, ROC.

出版信息

Eur J Nutr. 2013 Apr;52(3):1089-98. doi: 10.1007/s00394-012-0416-3. Epub 2012 Jul 31.

DOI:10.1007/s00394-012-0416-3
PMID:22847641
Abstract

PURPOSE

Glutamine (Gln) is a nutrient with immunomodulatory effects in metabolic stressed conditions. This study investigated the effects of Gln on colonic-inflammatory-mediator expression and mucosal repair in mice with dextran sulfate sodium (DSS)-induced colitis.

METHODS

C57BL/6 mice received distilled water containing 3 % DSS for 5 d to induce colitis. One of the DSS-treated groups was intraperitoneally injected with an alanyl (Ala)-Gln solution 3 days before (G-DSS) while the other group was administered Ala-Gln 3 days after colitis (DSS-G) was induced. The Ala-Gln solution provided 0.5 g Gln/kg/d. The saline-DSS group (S-DSS) received an identical amount of saline before and after colitis was induced to serve as a positive control.

RESULTS

The S-DSS group had a shorter colon length, higher plasma haptoglobin level, and more-severe colon inflammation. Also, the toll-like receptor (TLR)4 level, nuclear factor (NF)-κB activation, and inflammatory cytokine gene expression in the colon were higher than those of the normal control group. Gln administration either before or after colitis suppressed TLR4 protein levels, decreased plasma haptoglobin, and reduced colon inflammation. Histological inflammatory scores were also lowered. Compared to the post-colitis Gln group, preventive use of Gln had higher colon length, expressions of mucin 2, trefoil factor 3, and heat shock protein 72 genes were also upregulated in the colon.

CONCLUSIONS

These results suggest that Gln administered either before or after the colitis mitigated inflammation of colitis that was not observed in group without Gln injection. Prophylactic treatment with Gln had more-beneficial effects on reducing inflammatory markers and enhancing the recovery of mucosa in DSS-induced colitis.

摘要

目的

谷氨酰胺(Gln)是一种在代谢应激条件下具有免疫调节作用的营养素。本研究旨在探讨 Gln 对葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠结肠炎症介质表达和黏膜修复的影响。

方法

C57BL/6 小鼠饮用含 3% DSS 的蒸馏水 5 天以诱导结肠炎。DSS 处理组中的一组在结肠炎诱导前 3 天腹腔内注射丙氨酰(Ala)-Gln 溶液(G-DSS 组),另一组在结肠炎诱导后 3 天给予 Ala-Gln(DSS-G 组)。Ala-Gln 溶液提供 0.5 g Gln/kg/d。盐水-DSS 组(S-DSS 组)在诱导结肠炎前后给予等量生理盐水作为阳性对照。

结果

S-DSS 组的结肠长度较短,血浆触珠蛋白水平较高,结肠炎症较严重。此外,TLR4 水平、核因子(NF)-κB 激活以及结肠中炎症细胞因子基因表达均高于正常对照组。在结肠炎发生前后给予 Gln 均可抑制 TLR4 蛋白水平,降低血浆触珠蛋白水平,减轻结肠炎症。组织学炎症评分也降低。与结肠炎后 Gln 组相比,预防性使用 Gln 可使结肠长度更长,结肠中黏蛋白 2、三叶因子 3 和热休克蛋白 72 基因的表达也上调。

结论

这些结果表明,在没有 Gln 注射的情况下,Gln 无论是在结肠炎发生前还是发生后给予,均可减轻结肠炎的炎症。预防性 Gln 治疗对减轻 DSS 诱导的结肠炎中的炎症标志物和增强黏膜恢复具有更有益的作用。

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