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首页> 外文期刊>Evidence-based complementary and alternative medicine: eCAM >Xiaoyaosan Exerts Therapeutic Effects on the Colon of Chronic Restraint Stress Model Rats via the Regulation of Immunoinflammatory Activation Induced by the TLR4/NLRP3 Inflammasome Signaling Pathway
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Xiaoyaosan Exerts Therapeutic Effects on the Colon of Chronic Restraint Stress Model Rats via the Regulation of Immunoinflammatory Activation Induced by the TLR4/NLRP3 Inflammasome Signaling Pathway

机译：小姚桑斯通过调节TLR4 / NLRP3炎性信号通路诱导的免疫炎症激活的调节对慢性约束应力模型大鼠结肠进行治疗作用

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Depression is the neurological manifestation most commonly associated with gastrointestinal diseases. The release of inflammatory cytokines mediated by TLR4/NLRP3 inflammasome signaling-induced immunoinflammatory activation may represent a common pathogenic process underlying the development of gastrointestinal diseases and depression. Clinical studies have indicated that Xiaoyaosan (XYS) can relieve depressive behavior by improving gastrointestinal symptoms. We previously demonstrated that XYS can reduce colonic inflammation in a rat model of chronic unpredictable mild stress; however, the precise anti-inflammatory mechanisms involved remain unclear. Here, we investigated whether XYS can ameliorate depressive behavior through regulating the TLR4/NLRP3 inflammasome signaling pathway, thereby inhibiting immunoinflammatory activation and reducing colonic proinflammatory cytokine levels. Fifty-two healthy male Sprague–Dawley rats were randomly divided into four groups (control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to generate a model of stress-induced depression. XYS and fluoxetine were administered intragastrically. Behavioral changes in the rats were assessed after 21 days. Serum and colon samples were collected, and the relative levels of the inflammation indicators IL-6, IL-1 β , and TNF- α were determined by ELISA. Pathological changes in colon tissue were assessed by hematoxylin and eosin staining. The levels of TLR4, MyD88, NF- κ B-p65, TAK1, IRAK1, and TRAF6 were detected by immunohistochemistry, while the gene and protein expression levels of TLR4, MyD88, NF- κ B-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 were detected by quantitative polymerase chain reaction (qPCR) and Western blotting. The results indicated that XYS could improve the depressive-like behavior and the weight loss of rats with stress-induced depression. Furthermore, depressed rats treated with XYS exhibited decreased expression levels of TLR4, MyD88, NF- κ B-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 in colonic tissue; reduced colon and serum concentrations of the inflammatory factors IL-6, IL-1 β , and TNF- α ; and lowered levels of colonic inflammation.
机译：抑郁是最常见的胃肠疾病的神经系统表现。由TLR4 / NLRP3炎性信号诱导的免疫炎症激活介导的炎症细胞因子的释放可以代表胃肠道疾病和抑郁症的常见致病过程。临床研究表明，Xiaoyaosan（XYS）可以通过改善胃肠道症状来缓解抑郁行为。我们之前证明了XYS可以降低慢性不可预测的温和胁迫的大鼠模型中的结肠炎症;然而，涉及的精确的抗炎机制仍然不清楚。在这里，我们研究了Xys是否可以通过调节TLR4 / NLRP3炎性信号传导途径来改善抑郁行为，从而抑制免疫炎症激活和减少结肠促炎细胞因子水平。五十二个健康的雄性Sprague-Dawley大鼠随机分为四组（对照，模型，XYS和氟西汀）。后两组慢性约束应激的21天进行21天，以产生应激诱导的抑郁症的模型。 Xys和Flyoxetine胃内施用。 21天后评估大鼠的行为变化。收集血清和结肠样品，并通过ELISA测定炎症指示剂IL-6，IL-1β和TNF-α的相对水平。通过苏木精和曙红染色评估结肠组织的病理变化。免疫组织化学检测TLR4，MYD88，NF-κB-P65，TAK1，IRAK1和TRAF6的水平，而TLR4，MYD88，NF-κB-P65，TAK1，IRAK1，TRAF6，通过定量聚合酶链反应（QPCR）和Western印迹检测NLRP3，ASC和Caspase-1。结果表明，XYS可以改善抑郁样行为和应激抑制大鼠的重量损失。此外，用X细胞呈现的抑郁大鼠表现出TLR4，MyD88，NF-κB-P65，TAK1，IRAK1，TRAF6，NLRP3，ASC和Caspase-1的表达水平降低;减少结肠和炎症因子IL-6，IL-1β和TNF-α的血清浓度;降低结肠炎症水平。

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