β-葡聚糖通过促进胰高血糖素样肽-1分泌减轻肠缺血再灌注损伤

王维; 韩奔; 孙力华; 谢会超; 曾雄; 肖卫东; 王建

doi:10.16016/j.2097-0927.202409020

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β-葡聚糖通过促进胰高血糖素样肽-1分泌减轻肠缺血再灌注损伤

基础医学 | 更新时间：2025-01-23

- β-葡聚糖通过促进胰高血糖素样肽-1分泌减轻肠缺血再灌注损伤
- β-glucan attenuates intestinal ischemia-reperfusion injury in mice by promoting glucagon-like peptide-1 secretion
- 陆军军医大学学报 2025年47卷第2期页码：112-121
- 作者机构：
  
  1.陆军军医大学（第三军医大学）第二附属医院，营养科，重庆
  2.陆军军医大学（第三军医大学）第二附属医院，普通外科，重庆
- 作者简介：
  
  肖卫东，E-mail： xiaoweidong@tmmu.edu.cn
  王建，E-mail： wangjian_xq@tmmu.edu.cn
- 基金信息：
  
  国家自然科学基金面上项目(82270585)
- DOI：10.16016/j.2097-0927.202409020
  中图分类号： R364.12;R574;R977.6
- 纸质出版日期：2025-01-30，
  
  收稿日期：2024-09-05，
  
  修回日期：2024-10-16，
- 稿件说明：
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王维, 韩奔, 孙力华, 等. β-葡聚糖通过促进胰高血糖素样肽-1分泌减轻肠缺血再灌注损伤[J]. 陆军军医大学学报, 2025,47(2):112-121.

WANG WEI, HAN BEN, SUN LIHUA, et al. β-glucan attenuates intestinal ischemia-reperfusion injury in mice by promoting glucagon-like peptide-1 secretion. [J]. Journal of army medical university, 2025, 47(2): 112-121.
王维, 韩奔, 孙力华, 等. β-葡聚糖通过促进胰高血糖素样肽-1分泌减轻肠缺血再灌注损伤[J]. 陆军军医大学学报, 2025,47(2):112-121. DOI： 10.16016/j.2097-0927.202409020.

WANG WEI, HAN BEN, SUN LIHUA, et al. β-glucan attenuates intestinal ischemia-reperfusion injury in mice by promoting glucagon-like peptide-1 secretion. [J]. Journal of army medical university, 2025, 47(2): 112-121. DOI： 10.16016/j.2097-0927.202409020.

摘要

目的

探讨β-葡聚糖（β-glucan， BG）通过调控胰高血糖素样肽-1（glucagon-like peptide-1，GLP-1）分泌对肠缺血再灌注（intestinal ischemia reperfusion， II/R）损伤作用及机制。

方法

将18只6～8周雄性C57BL/6小鼠按随机数字表法分为3组（

=6）：假手术组、II/R组、II/R+BG组，假手术组和II/R组正常饮食，II/R+BG组造模前2周饮用水中含0.1 mg/mL BG，建模后，HE染色用于观察肠道形态变化，RT-qPCR评估与肠道屏障损伤相关的分子（Occludin、ZO-1和Claudin-1）。将12只6～8周龄雄性C57BL/6小鼠按随机数字表法分为2组（

=6）：Water组、BG组，Water组正常饮食，BG组饮用水含中0.1 mg/mL BG。分别用ELISA、免疫荧光法以及RT-PCR检测与GLP-1表达相关的分子（Gcg、Pcsk1/2、GIP和Foxa2），探究0.1mg/mL BG治疗对正常小鼠血清和肠组织中GLP-1水平的影响。将另外12只6～8周龄雄性C57BL/6小鼠按随机数字表法分为2组（

=6）：II/R组造模前腹腔注射生理盐水，连续3 d，每12 h注射1次，II/R+利拉鲁肽（liraglutide， LLT）组造模前腹腔注射0.2 μg/g LLT，连续3 d，每12 h注射1次，建模后，HE染色用于观察肠道形态变化，RT-qPCR和Western印迹用于评估与肠道屏障损伤相关的分子（Occludin、ZO-1和Claudin-1）。12只6～8周龄雄性C57BL/6小鼠饮水中加入BG预处理2周，按随机数字表法分为2组（

=6）：II/R+BG组、II/R+BG+Ex9-39（GLP-1R拮抗剂）组（建模前1 h腹膜注射2 μg/g Ex9-39），造模后采用上述方法评估肠屏障损伤情况。

结果

与假手术组相比，II/R组诱导Occludin、ZO-1和Claudin-1的mRNA水平显著降低，Chiu’s评分升高（

0.05）。而II/R+BG组3种分子的mRNA水平明显高于II/R组，Chiu’s评分低于II/R组（

0.05）。与Water组相比，BG组显著增强了正常小鼠血清和肠道中GLP-1的分泌，并改善了GLP-1相关分子的mRNA表达（

0.05）。GLP-1类似物LLT的干预可以减轻II/R损伤，降低Chiu’s评分，与II/R组相比有统计学差异（

0.05）。与II/R+BG组相比，II/R+BG+Ex9-39（GLP-1R拮抗剂）组逆转了BG预处理对II/R损伤的保护作用，在Occludin、ZO-1和Claudin-1的表达以及Chiu’s评分方面存在统计学差异（

0.05）。

结论

BG可以通过促进肠道GLP-1分泌减轻II/R后肠黏膜形态和功能损伤。

Abstract

Objective‍　‍To investigate the protective effect of β-glucan (BG) against intestinal ischemia reperfusion (II/R) injury by regulating the secretion of glucagon-like peptide-1 (GLP-1). Methods‍　‍Male C57BL/6 mice (6~8 weeks old) were subjected

and finally

the experiments had sham group

II/R group

II/R+BG group (0.1 mg/mL BG in drinking water for 2 weeks before modeling)

II/

R+liraglutide (LLT

GLP-1 analogue) group (0.2 μg/g LLT injected every 12 hours for 3 consecutive days before modeling)

and II/R+BG+Ex9-39 (GLP-1R antagonist) group (intraperitoneal injection of 2 μg/g Ex9-39 1 h before modeling). After modeling

HE staining was used to observe intestinal morphological changes

and RT-qPCR and Western blotting were employed to evaluate the molecules (Occludin

ZO-1 and Claudin-1) related to intestinal barrier damage. The effect of 0.1 mg/mL BG treatment on the GLP-1 level in the serum and intestinal tissues of normal mice was determined with ELISA and immunofluorescence assay

respectively

and RT-PCR for the molecules related to GLP-1 expression (Gcg

Pcsk1/2

GIP and Foxa2). The effects of LLT and Ex9-39 pretreatment on intestinal morphology and intestinal barrier damage were also determined by morphological observation and expression levels of related molecules. Results‍　‍II/R induced significant decreases in the mRNA levels of Occludin

ZO-1 and Claudin-1 and increase in Chiu's score when compared with sham control mice (

0.05). While

the mRNA levels of the 3 molecules were obviously higher and the Chiu's score was lower in the II/R+BG group than the II/R group (

0.05). BG pretreatment induced notably enhanced secretion of GLP-1 in the serum and intestinal tract of normal mice

and improved the mRNA expression of GLP-1-related molecules (

0.05). The intervention of GLP-1 analogue LLT could attenuate the II/R damage and decreased Chiu's score

with statistical difference in comparison with the II/R group (

0.05). GLP-1 receptor antagonist Ex9-39 reversed the protective effects of BG pretreatment against II/R damage

with notably differences in the expression of Occludin

ZO-1 and Claudin-1 and Chiu's score (

0.05). Conclusion‍　‍BG can attenuate intestinal mucosal and functional injury after II/R by promoting intestinal GLP-1 secretion.

关键词

肠缺血再灌注损伤β-葡聚糖GLP-1肠屏障

Keywords

intestinal ischaemia-reperfusion injuryβ-glucanglucagon-like peptide-1intestinal barrier

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