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.
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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逍遥散通过调节TLR4/NLRP3炎症小体信号通路诱导的免疫炎症激活对慢性束缚应激模型大鼠结肠产生治疗作用
DOI：
10.1155/2021/6673538
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Chen JX
中科院分区：
文献类型：
--
作者：
Zhu HZ;Liang YD;Hao WZ;Ma QY;Li XJ;Li YM;Chen JX
抑郁症是最常见的与胃肠道疾病相关的神经系统表现。TLR 4/NLRP 3炎性体信号介导的免疫炎症激活介导的炎性细胞因子的释放可能代表了胃肠道疾病和抑郁症发展的共同致病过程。临床研究表明逍遥散可通过改善胃肠道症状来缓解抑郁行为。我们先前证明XYS可以减少慢性不可预测的轻度应激大鼠模型中的结肠炎症;然而，所涉及的确切抗炎机制仍不清楚。在这里，我们研究XYS是否可以通过调节TLR 4/NLRP 3炎症信号通路来改善抑郁行为，从而抑制免疫炎症激活并降低结肠促炎细胞因子水平。将52只健康雄性SD大鼠随机分为4组（对照组、模型组、消郁饮组和氟西汀组）。后三组进行21天的慢性束缚应激，以产生应激性抑郁模型。XYS和氟西汀灌胃给药。21天后评估大鼠的行为变化。收集血清和结肠标本，采用ELISA法测定炎症指标IL-6、IL-1β和TNF-α的相对水平。苏木精-伊红染色观察结肠组织病理变化。采用免疫组化法检测TLR 4、MyD 88、NF-κB-p65、TAK 1、IRAK 1、TRAF 6的表达水平;采用定量聚合酶链反应（qPCR）和Western blotting法检测TLR 4、MyD 88、NF-κB-p65、TAK 1、IRAK 1、TRAF 6、NLRP 3、ASC、caspase-1的基因和蛋白表达水平。结果表明，消郁饮能改善应激抑郁模型大鼠的抑郁样行为和体重减轻。此外，XYS治疗的抑郁大鼠结肠组织中TLR 4、MyD 88、NF-κB-p65、TAK 1、IRAK 1、TRAF 6、NLRP 3、ASC和caspase-1的表达水平降低;结肠和血清中炎症因子IL-6、IL-1β和TNF-α的浓度降低;结肠炎症水平降低。
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-1β, 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-κB-p65, TAK1, IRAK1, and TRAF6 were detected by immunohistochemistry, while the gene and protein expression levels of TLR4, MyD88, NF-κB-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-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 in colonic tissue; reduced colon and serum concentrations of the inflammatory factors IL-6, IL-1β, and TNF-α; and lowered levels of colonic inflammation.
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影响因子：
3.4
作者：
Fu, Songnian;Wang, Jiangtao;Jiang, Sheng
通讯作者：
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影响因子：
4.7
作者：
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15.1
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影响因子：
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