CHEN Li, WANG Bochao, GAN Yingqi, HE Xiaoyu, TAN Zhijun, WANG Dongqiang
Current Immunology. 2025, 45(3): 297-303.
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The aim of the study was to investigate the effect of alpinetin on intestinal barrier damage in septic rats through regulating the stimulator of interferon gene (STING)/TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) signaling pathway. Rats were randomly divided into the sepsis group, the alpinetin group, the STING agonist (ADU-S100) group, the alpinetin+ADU-S100 group, and the blank control group, with 18 rats per group. Except the control group, sepsis model was established by cecal ligation and perforation procedure. After successful modeling, corresponding drugs were given once a day for 2 w. The serum level of fluorescein isothiocyanate FITC-glucan in each group was detected. H-E staining was used to evaluate the histopathological injury of small intestine. The expression of zonula occluden 1 (ZO-1) and Occludin in the small intestine was detected by immunohistochemical staining. Mean fluorescence intensity (MFI) of CD86 and CD206 in small intestine tissues was detected by immunofluorescence staining. The levels of TNF-α, IL-6, and IL-10 in the small intestine were detected by ELISA. Western blotting was used to detect the protein levels of STING, p-TBK1, and p-IRF3 in small intestine tissues. The results showed that compared to those of the control group, serum FITC-glucan level, small intestine mucosal Chiu score, CD86 MFI, TNF-α, IL-6 levels and STING, p-TBK1, p-IRF3 protein expressions in small intestinal tissues of sepsis rats were all increased, while the numbers of ZO-1 and Occludin positive cells, CD206 MFI, and IL-10 levels in the small intestine were significantly decreased (all with P<0.001). Compared to those of the sepsis group, serum FITC-glucan level, small intestine mucosal Chiu score, CD86 MFI, TNF-α, IL-6 levels, and STING, p-TBK1, p-IRF3 protein expressions in small intestinal tissues of the alpinetin group were all decreased, while the numbers of ZO-1 and Occludin positive cells in the small intestine, and the levels of CD206 MFI and IL-10 were increased (all with P<0.001). The dynamic trend of the above indexes in ADU-S100 group was opposite to those in the alpinetin group (all with P<0.001). ADU-S100 partially reversed the improvement of intestinal barrier damage in medicated sepsis rats (all with P<0.001). Therefore, the underlying mechanism of alpinetin in improving intestinal barrier damage in sepsis rats is closely associated with its inhibition of the STING/TBK1/IRF3 pathway.