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β-glucan attenuates intestinal ischemia-reperfusion injury in mice by promoting glucagon-like peptide-1 secretion
Journal of Army Medical University 2025, 47(2): 112-121
Published: 30 January 2025
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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 (P<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 (P<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 (P<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 (P<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 (P<0.05).

Conclusion

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

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