Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
BMC Complement Altern Med. 2019 Nov 27;19(1):337. doi: 10.1186/s12906-019-2749-4.
BACKGROUND: Tong-Xie-Yao-Fang (TXYF) has been shown to be effective in diarrhoea-predominant irritable bowel syndrome (IBS-D) patients. However, the underlying mechanism remains to be clarified. The aim of this study was to investigate the efficacy and related mechanisms of TXYF in an IBS-D rat model. METHODS: The IBS-D rat model was established with 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. Then, IBS-D rats were divided into control, TXYF and rifaximin groups and treated intragastrically with normal saline, TXYF and rifaximin, respectively, for 14 days. The following indicators were measured before and after treatment: defecation frequency, faecal water content (FWC) and colorectal distension (CRD). Histopathological changes in the distal colon were observed after treatment. The expression of OCLN and ZO1 in the distal colon of IBS-D rats reflected the intestinal mucosal permeability, as measured by qRT-PCR, western blot, and enzyme-linked immunosorbent assays (ELISAs). The NF-κB and Notch signalling pathways and inflammation-related factors were investigated. RESULTS: After treatment with TXYF, the defecation frequency, FWC and CRD were significantly lower than those in the model group (P < 0.05). HE staining showed that colonic epithelial cells (CECs) in the IBS-D rats displayed significant oedema, impaired intestinal mucosal integrity and an increased influx of inflammatory cells. A significant reduction in granulocyte and CEC oedema was observed after the administration of TXYF and rifaximin compared to that of the model group and blank group (P < 0.05). TXYF significantly upregulated the expression of OCLN and ZO-1 and downregulated inflammation-related factors (IL-6, IL-1β, and TNF-α and the chemokine KC) in IBS-D rats compared to those in the model group rats (P < 0.05). In terms of the NF-κB and Notch signalling pathways, the expression of NICD, p-ERK, Hes-1 and p-P65 decreased significantly in the TXYF and rifaximin groups, while the expression of ATOH1 increased significantly compared to that in the model group (P < 0.05). CONCLUSION: TXYF can effectively improve intestinal permeability and enhance intestinal mucosal barrier function, which may be related to inhibition of the inflammatory cascade and the NF-κB and Notch signalling pathways.
背景：痛泻要方（TXYF）已被证明对腹泻型肠易激综合征（IBS-D）患者有效。然而，其潜在机制仍有待阐明。本研究旨在探讨 TXYF 在 IBS-D 大鼠模型中的疗效及其相关机制。
方法：采用 4%醋酸法建立 IBS-D 大鼠模型，并用苏木精-伊红（HE）染色进行评价。然后，将 IBS-D 大鼠分为对照组、TXYF 组和利福昔明组，分别给予生理盐水、TXYF 和利福昔明灌胃治疗 14 天。治疗前后分别测量大鼠的排便频率、粪便含水量（FWC）和结肠扩张（CRD）。治疗后观察大鼠远端结肠的组织学变化。采用 qRT-PCR、western blot 和酶联免疫吸附试验（ELISA）检测大鼠远端结肠 OCLN 和 ZO1 的表达，反映肠道黏膜通透性。同时还研究了 NF-κB 和 Notch 信号通路以及炎症相关因子。
结果：TXYF 治疗后，大鼠的排便频率、FWC 和 CRD 均明显低于模型组（P<0.05）。HE 染色显示，IBS-D 大鼠的结肠上皮细胞（CECs）出现明显水肿，肠黏膜完整性受损，炎症细胞浸润增加。与模型组和空白组相比，TXYF 和利福昔明治疗后粒细胞和 CEC 水肿明显减轻（P<0.05）。与模型组大鼠相比，TXYF 能显著上调 OCLN 和 ZO-1 的表达，下调 IBS-D 大鼠的炎症相关因子（IL-6、IL-1β、TNF-α 和趋化因子 KC）的表达（P<0.05）。在 NF-κB 和 Notch 信号通路方面，TXYF 和利福昔明组的 NICD、p-ERK、Hes-1 和 p-P65 表达明显下降，而 ATOH1 表达明显升高，与模型组相比差异有统计学意义（P<0.05）。
结论：TXYF 能有效改善肠道通透性，增强肠道黏膜屏障功能，其机制可能与抑制炎症级联反应和 NF-κB、Notch 信号通路有关。
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