小檗碱可预防应激引起的肠道炎症和内脏敏化，并降低大鼠的肠道蠕动。

BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM: To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS: IBS was induced in rats water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of C-kit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB. RESULTS: WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION: BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.

背景：肠易激综合征（IBS）是一种常见的慢性非器质性消化系统疾病。小檗碱（BBR）已被用于治疗 IBS 患者，但潜在的治疗机制尚不清楚。我们认为 BBR 通过预防应激性肠道炎症和内脏高敏性以及降低肠道蠕动来发挥其治疗作用。

目的：验证 BBR 通过预防肠道黏膜亚临床炎症、降低内脏高敏性和肠道蠕动来发挥其对 IBS 的治疗作用的假说。

方法：采用水回避应激（WAS）诱导大鼠 IBS。分别采用 qRT-PCR 和组织学分析评估细胞因子和黏膜炎症水平。改良 ELISA 和 qRT-PCR 用于评估核因子 kappa-B（NF-κB）信号转导通路。结肠扩张试验、胃肠道转运测量、Western blot 和 qRT-PCR 用于分析内脏敏感性、肠道蠕动、C-kit（Cajal 间质细胞标志物）的表达以及脑源性神经营养因子（BDNF）及其受体 TrkB 的表达。

结果：WAS 导致黏膜炎症、内脏痛觉过敏和高肠道蠕动。口服 BBR 抑制 NF-κB 信号转导通路，减少促炎细胞因子（IL-1β、IL-6、干扰素-γ和肿瘤坏死因子-α）的表达，促进抗炎细胞因子（IL-10 和转化生长因子-β）的表达，并改善末端回肠组织炎症。BBR 抑制 IBS 大鼠中 BDNF、TrkB 和 C-kit 的表达，导致肠道蠕动和内脏高敏性降低。高剂量（100mg/kg）BBR 的治疗效果优于低剂量（25mg/kg）组。

结论：BBR 通过抑制 IBS 大鼠肠道 NF-κB 信号通路减轻肠道黏膜炎症。BBR 降低 BDNF、其受体 TrkB 和 C-kit 的表达。BBR 还降低肠道蠕动和内脏敏感性，从而发挥其对 IBS 的治疗作用。