Abstract
Background
Intestinal mucosal barrier dysfunction plays a crucial role in the pathogenesis of irritable bowel syndrome with diarrhea (IBS-D). In order to explore the mechanism of electroacupuncture (EA) treatment on intestinal mucosal barrier, this study observed the effect of EA on aquaporins (AQPs), tight junctions (TJs), NF-κB pathway and the gut microbiota in IBS-D rats.
Methods
The IBS-D model was established by acetic acid enema combined with chronic restraint method. The effects of EA on the treatment of IBS-D were examined by the abdominal withdrawal reflex score, Bristol's fecal character score, fecal water content, small intestine propulsion rate and HE staining. AQPs, TJs and inflammation-related molecular mechanisms were explored. The fecal samples were applied for 16S rRNA sequencing to assess the effect of EA intervention to the intestinal bacterial abundance.
Results
EA reduced intestinal sensitization, restored intestinal motility and improved inflammatory cell infiltration. Furthermore, EA improved intestinal inflammation and flora environment significantly, inhibited NF-κB signaling and inflammatory factors (IL-1β and TNF-α). It can also increase the gene and protein expression of AQPs (AQP1, AQP3, and AQP8) and the gene levels of TJs (ZO-1 and Occludin).
Conclusion
EA has an inhibitory effect on the NF-κB signaling pathway, and regulates the proteins of AQP1, AQP3, AQP8, and TJs to restore the balance of water metabolism and intestinal permeability in IBS-D, which also restored the function of the intestinal mucosa by regulating the intestinal flora.
Graphical Abstract
Irritable bowel syndrome with predominant diarrhea (IBS-D) is a common gastrointestinal disease in clinical practice, which was affected by intestinal mucosal barrier dysfunction, intestinal mucosal inflammation production and abnormal intestinal flora, then there is currently no specific drug for treating IBS-D. Electroacupuncture (EA), as a non-pharmacological therapy, has good therapeutic effects in treating IBS-D. Aquaporins (AQPs) are distributed in the intestinal mucosa of the intestine and are important factors in mediating water–liquid transmembrane transport. Changes in AQPs expression have been identified as a common factor in the etiology of certain gastrointestinal diseases. AQP1, AQP3, and AQP8 are distributed in the distal colon. EA can inhibit NF-κB signaling pathway, and regulate the proteins of AQP1, AQP3, AQP8, and TJs to restore the balance of water metabolism and intestinal permeability in IBS-D, which also can restore the function of the intestinal mucosa by regulating the intestinal flora.
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Acknowledgments
This research was supported by New Teacher Initiation Fund Project of Beijing University of Chinese Medicine (No. 2020-JYB-XJSJJ-016).
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Yemao Chai, Xiaoxuan Ren and Honglin Zhang conceived and designed the study. Xueling Kang, Xiaying Li and Zhansheng Huang performed the experiments; Kai Zhang and Yuanyuan Li performed the statistical analysis of the data; Yemao Chai and Xueling Kang wrote the manuscript. All authors have read and approved the manuscript.
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The animal study was reviewed and approved by Animal Ethics Committee, Beijing University of Chinese Medicine, China (Permission number BUCM-1–2020100701-0013).
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Kang, X., Zhang, H., Li, X. et al. Electroacupuncture Improving Intestinal Barrier Function in Rats with Irritable Bowel Syndrome Through Regulating Aquaporins. Dig Dis Sci 69, 1143–1155 (2024). https://doi.org/10.1007/s10620-024-08288-x
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DOI: https://doi.org/10.1007/s10620-024-08288-x