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.

中文翻译：

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电针通过调节水通道蛋白改善肠易激综合征大鼠肠道屏障功能

背景

肠粘膜屏障功能障碍在腹泻性肠易激综合征（IBS-D）的发病机制中起着至关重要的作用。为了探讨电针（EA）治疗对肠粘膜屏障的作用机制，本研究观察了电针对IBS-D大鼠水通道蛋白（AQPs）、紧密连接（TJs）、NF-κB通路和肠道菌群的影响。

方法

采用醋酸灌肠联合慢性束缚法建立IBS-D模型。通过腹部撤退反射评分、Bristol粪便性状评分、粪便含水量、小肠推进率和HE染色检查电针治疗IBS-D的效果。探索了 AQP、TJ 和炎症相关的分子机制。对粪便样本进行 16S rRNA 测序，以评估 EA 干预对肠道细菌丰度的影响。

结果

电针可降低肠道敏感性，恢复肠道蠕动并改善炎症细胞浸润。此外，EA可显着改善肠道炎症和菌群环境，抑制NF-κB信号传导和炎症因子（IL-1β和TNF-α）。它还可以增加 AQP（AQP1、AQP3 和 AQP8）的基因和蛋白质表达以及 TJ（ZO-1 和 Occludin）的基因水平。

结论

EA对NF-κB信号通路有抑制作用，调节AQP1、AQP3、AQP8和TJs蛋白，恢复IBS-D中水代谢和肠道通透性的平衡，从而恢复肠粘膜功能通过调节肠道菌群。

图形概要

腹泻型肠易激综合征（IBS-D）是临床上常见的胃肠道疾病，受肠粘膜屏障功能障碍、肠粘膜炎症产生和肠道菌群异常影响，目前尚无治疗IBS-D的特效药物。电针（EA）作为一种非药物疗法，对于治疗IBS-D具有良好的治疗效果。水通道蛋白（AQP）分布在肠道粘膜中，是介导水-液跨膜转运的重要因子。AQP 表达的变化已被确定为某些胃肠道疾病病因学的常见因素。AQP1、AQP3和AQP8分布于远端结肠。电针可抑制NF-κB信号通路，调节AQP1、AQP3、AQP8和TJs蛋白，恢复IBS-D水代谢和肠道通透性的平衡，从而通过调节肠道菌群。