目的 明确芍药总苷对肠易激综合征(IBS)的治疗效果,并初步探究芍药总苷改善IBS腹痛腹泻症状的分子机制。方法 采用束缚应激刺激和皮下注射新斯的明法分别构建大鼠腹泻和小鼠腹痛模型,基于上述2种模型考察不同剂量芍药总苷对腹痛腹泻症状的改善效果。采用胰蛋白酶、白介素-1β(IL-1β)刺激法分别构建肠上皮Caco-2细胞屏障功能紊乱模型及Caco-2细胞炎症模型,并通过上述模型初步探索芍药总苷对肠上皮细胞状态和功能的调控作用。结果 芍药总苷显著降低腹泻模型大鼠的排便频率,且明显改善腹痛模型小鼠的肠异常蠕动。Caco-2功能紊乱模型经芍药总苷处理后,上皮细胞电阻(TEER)值显著升高;荧光黄透过率显著降低;紧密连接蛋白(ZO-1)的表达量明显上调。Caco-2炎症模型经芍药总苷处理后,核因子抑制蛋白-κB(IκBα)的表达水平显著升高。结论 芍药总苷通过改善受损的肠上皮细胞屏障功能及抑制炎症反应,从而有效改善肠易激综合征的腹痛与腹泻症状。
Abstract
OBJECTIVE To clarify the effect of total glucosides from paeony(PTG) on irritable bowel syndrome (IBS), and to explore the molecular mechanism of PTG on alleviating diarrhea symptoms and abdominal pain.METHODS The diarrhea model was conducted by exposing rat to restraint stress stimulation and bellyache model was conducted by subcutaneous injection of neostigmine to mice. Based on these two models, the curative effect of PTG on IBS was investigated. To investigate the regulative effects of PTG on Caco-2 cells, the Caco-2 monolayer cell model with barrier dysfunction was established by trypsin stimulation, and the inflammatory Caco-2 cell model was established by interleukin-1β (IL-1β) stimulation.RESULTS PTG could significantly reduce the frequency of defecation in diarrhea rat model (P<0.05) and relieve abnormal bowel movements in bellyache mice model (P<0.05). After PTG treatment, the TEER value of Caco-2 monolayer was significantly increased (P<0.01), the transmittance of fluorescence yellow was significantly decreased (P<0.001) and the expression of tight junction (ZO-1)protein was notably up-regulated (P<0.001). In addition, the gene and protein expression of nuclear factor profilin kappa B(IκBα)in inflammatory Caco-2 cell model was significantly improved (P<0.001) after PTG treatment.CONCLUSION PTG significantly ameliorates IBS symptoms by protecting the barrier function of Caco-2 cell monolayer and relieving inflammation of Caco-2 cells.
关键词
肠易激综合征 /
芍药总苷 /
腹泻 /
腹痛 /
Caco-2细胞功能 /
炎症
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Key words
irritable bowel syndrome /
Paeonia lactiflora total glucosides /
diarrhea symptoms /
abdominal pain /
Caco-2 cell function /
inflammation
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中图分类号：
R285
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参考文献
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脚注
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基金
国家自然科学基金项目资助(81573683,81773803)
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