Glucagon-like peptide-2 improves intestinal immune function and diminishes bacterial translocation in a mouse model of parenteral nutrition
Glucagon-like peptide-2 improves intestinal immune function and diminishes bacterial translocation in a mouse model of parenteral nutrition
复制标题
胰高血糖素样肽 2 可以改善肠外营养小鼠模型中的肠道免疫功能并减少细菌移位。
DOI：
10.1016/j.nutres.2017.10.007
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发表时间：
2018-01-01
影响因子：
4.5
通讯作者：
Wang, Xinying
中科院分区：
文献类型：
--
作者：
Lei, Qiucheng;Bi, Jingcheng;Wang, Xinying
肠外营养（PN）与肠道免疫力受损导致的感染风险增加有关。胰高血糖素样肽-2（GLP-2）虽然能增强肠道屏障功能，但其是否能改善粘膜免疫屏障功能尚不清楚。我们假设，用GLP-2注射PN小鼠模型可以改善先天性和获得性免疫，并防止细菌移位。静脉插管后48小时，将癌症研究所的雄性小鼠随机分为3组，基于它们的饮食，提供盐水（n = 10）、PN（n = 9）或PN + GLP-2（30 μ g bid/小鼠，n = 10）5天。与普通饲料相比，PN降低了IL-4和IL-13水平（P <0.05，分别），而与单独PN相比，GLP-2注射增加了IL-4和IL-13水平（P <0.05，分别）。与普通饲料相比，PN显著抑制了分泌型磷脂酶A2和cryptdin-4的表达，而GLP-2改善了分泌型磷脂酶A2和cryptdin-4的表达。与普通饲料相比，PN显著降低了溶菌酶和多聚免疫球蛋白受体水平，而与PN相比，GLP-2显著增加了这些蛋白水平（分别为P <0.01）。在组织和管腔样本中，与食物相比，PN降低了分泌型免疫球蛋白A水平（P < .05），而与单独PN相比，GLP-2增加了分泌型免疫球蛋白A水平（P < .05）。在功能上，与食物组相比，在PN组中观察到更多的细菌移位（P < .001），并且GLP-2注射降低了细菌移位至食物水平（P < .05）。总之，GLP-2治疗可改善肠内先天性和获得性免疫，并预防全胃肠外营养小鼠的细菌移位。(C)2017爱思唯尔公司All rights reserved.
Parenteral nutrition (PN) is associated with increased infectious risks due to impaired intestinal immunity. Although glucagon-like peptide-2 (GLP-2) enhances the gut barrier function, it is uncertain whether it improves mucosal immunologic barrier function. We hypothesized that injecting the PN mouse model with GLP-2 improved innate and acquired immunity, and prevented bacterial translocation. Forty-eight hours after venous cannulation, male Institute of Cancer Research mice were randomly divided into 3 groups based on their diet chow with saline (n = 10), PN (n = 9), or PN + GLP-2 (30 mu g bid per mouse, n = 10) provided for 5 days. Compared with chow, PN reduced interleukin (IL)-4 and IL-13 levels (P < .05, respectively), whereas, compared with PN alone, GLP-2 injection increased IL-4 and IL-13 levels (P < .05, respectively). Compared with chow, PN considerably suppressed, whereas GLP-2 improved, secretory phospholipase A2 and cryptdin-4 expression. PN, compared with chow, considerably decreased lysozyme and polymeric immunoglobulin receptor levels, whereas, compared with PN, GLP-2 significantly increased these protein levels (P < .01, respectively). In tissue and luminal samples, compared with chow, PN reduced secretory immunoglobulin A levels (P < .05), whereas, compared with PN alone, GLP-2 increased secretory immunoglobulin A levels (P < .05). Functionally, more bacterial translocation was observed in the PN group compared with the chow group (P < .001), and GLP-2 injection decreased bacterial translocation to chow levels (P < .05). In summary, GLP-2 treatment may improve intestinal innate and acquired immunity, and prevent bacterial translocation in mice on total parenteral nutrition. (C) 2017 Elsevier Inc. All rights reserved.