School of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Int J Mol Sci. 2024 Sep 24;25(19):10262. doi: 10.3390/ijms251910262.
Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder and is strongly associated with an increased risk of depression and anxiety. The brain-gut axis plays an important role in the pathophysiologic changes in IBS, yet effective treatments for IBS are still lacking. Sinisan, originating from the by the medical sage Zhang Zhongjing, is a classic formula in the Eight Methods of Traditional Chinese Medicine (TCM) that focuses on dispersing the liver and regulating the spleen, relieving depression and transmitting evils, and has been widely used in the treatment of liver-depression and spleen-deficiency, diarrhea, and related liver and stomach disorders. However, the therapeutic effect of sinisan in IBS has not been clarified. The aim of this study was to investigate the effects of sinisan on stress-induced intestinal dysfunction and depressive behavior in IBS mice. We established a diarrhea-predominant irritable bowel syndrome (IBS-D) mouse model using a 4% acetic acid enema combined with restraint stress, and analyzed the results using behavioral tests, relevant test kits, hematoxylin-eosin (HE) staining, immunofluorescence (IF), Western blot (WB), and quantitative fluorescence polymerase chain reaction (qRT-PCR). The results showed that sinisan administration significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice, improved mild colonic inflammation and intestinal mucosal permeability, up-regulated the expression of tight junction proteins ZO-1 and occludin. Sinisan significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice by decreasing the expression of TNF-α, promoting the expression of tight junction proteins (occludin, ZO-1) expression, and inhibiting the Tlr4/Myd88 signaling pathway, thereby attenuating the inflammatory response, protecting the intestinal barrier, and alleviating symptoms in the IBS-D mouse model. Taken together, sinisan may ameliorate intestinal inflammation and the intestinal barrier by regulating 5-HT expression and the Tlr4/Myd88 pathway, thereby alleviating stress-induced intestinal dysfunction and depressive behaviors in IBS-D mice.
肠易激综合征（IBS）是一种常见的慢性功能性肠病，与抑郁和焦虑风险增加密切相关。脑-肠轴在 IBS 的病理生理变化中起着重要作用，但目前仍缺乏有效的 IBS 治疗方法。四逆散源于医学圣典《伤寒杂病论》，是中医八法中调肝理脾、解郁泻热、达邪外出的经典方剂，广泛应用于肝郁脾虚、腹泻及相关肝胃失调的治疗。然而，四逆散治疗 IBS 的疗效尚未明确。本研究旨在探讨四逆散对 IBS 应激诱导的肠道功能障碍和抑郁行为的影响。我们采用 4%醋酸灌肠联合束缚应激建立腹泻型肠易激综合征（IBS-D）小鼠模型，通过行为学测试、相关试剂盒、苏木精-伊红（HE）染色、免疫荧光（IF）、Western blot（WB）和实时荧光定量聚合酶链反应（qRT-PCR）进行分析。结果表明，四逆散可显著缓解 IBS-D 小鼠的肠道功能障碍和抑郁样行为，改善轻度结肠炎症和肠道黏膜通透性，上调紧密连接蛋白 ZO-1 和 occludin 的表达。四逆散通过降低 TNF-α的表达，促进紧密连接蛋白（occludin、ZO-1）的表达，抑制 Tlr4/Myd88 信号通路，缓解 IBS-D 小鼠的炎症反应，保护肠道屏障，从而缓解 IBS-D 小鼠的肠道功能障碍和抑郁样行为。综上所述，四逆散可能通过调节 5-HT 表达和 Tlr4/Myd88 通路，改善肠道炎症和肠道屏障，从而缓解 IBS-D 小鼠的应激诱导的肠道功能障碍和抑郁行为。
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