茯苓酸调节Jagged1/Notch1信号通路对慢性支气管炎大鼠炎症反应的影响

Effect of pachymic acid on inflammatory response in chronic bronchitis rats by regulating Jagged1/Notch1 signaling pathway

    摘要
  • 摘要:
    目的 探究茯苓酸调节Jagged1/Notch1信号通路对慢性支气管炎大鼠炎症反应的影响。
    方法 通过吸食2%二氧化硫诱导慢性支气管炎大鼠模型，将大鼠分为对照组、模型组、低剂量（L）-茯苓酸（7.5 mg/kg/d）组、高剂量（H）-茯苓酸（15 mg/kg/d）组和H-茯苓酸+Jagged1（50 mg/kg Jagged1蛋白）组，每组12只。测量大鼠0.3 s用力呼气量（FEV 0.3）、强制肺活量（FVC）和FEV 0.3/FVC比值；检测支气管肺泡洗涤液（BALF）中的细胞数量；苏木素-伊红（HE）染色分析肺组织病理学，血清白细胞介素17A（IL-17A）、IL-10、趋化因子C-C-基元配体20（CCL20）、C-C趋化因子受体6（CCR6）水平及肺组织中Jagged1和Notch1蛋白表达水平。
    结果 与对照组比较，模型组大鼠FEV 0.3、FVC和FEV 0.3/FVC降低，BALF中白细胞计数（WBC）、中性粒细胞计数（NEU）、淋巴细胞（Ly）、单核细胞（Mon）数量增加，肺上叶炎症浸润评分升高，血清IL-17A、CCL20和CCR6水平提高，IL-10水平降低，Jagged1和Notch1蛋白表达提高（P＜0.05）；与模型组比较，L-茯苓酸组、H-茯苓酸组大鼠FEV 0.3、FVC和FEV 0.3/FVC提高，BALF中WBC、NEU、Ly、Mon细胞数量减少，肺上叶炎症浸润评分降低，血清IL-17A、CCL20和CCR6水平降低，IL-10水平提高，Jagged1和Notch1蛋白表达降低（P＜0.05）；与H-茯苓酸组比较，H-茯苓酸+Jagged1组大鼠FEV 0.3、FVC和FEV 0.3/FVC降低，BALF中WBC、NEU、Ly、Mon细胞数量增加，肺上叶炎症浸润评分升高，血清IL-17A、CCL20和CCR6水平提高，IL-10水平降低，Jagged1和Notch1蛋白表达提高（P＜0.05）。
    结论 茯苓酸可能通过抑制Jagged1/Notch1信号通路减轻慢性支气管炎大鼠炎症反应。

     

    Abstract:
    OBJECTIVE To investigate the effect of pachymic acid on inflammatory response in chronic bronchitis rats by regulating Jagged1/Notch1 signaling pathway.
    METHODS A chronic bronchitis rat model was developed by inhalation of 2% sulfur dioxide. Rats were divided into control group, model group, low-dose （L）-pachymic acid （7.5 mg/kg/d） group, high-dose （H）-pachymic acid （15 mg/kg/d） group and H-pachymic acid + Jagged1 （50 mg/kg Jagged1 protein） group （each n=12）. Forced expiratory volume in 0.3 s （FEV 0.3）, forced vital capacity （FVC） and FEV 0.3/FVC ratio were measured. Cell counts in bronchoalveolar lavage fluid （BALF） were determined. Hematoxylin-eosin （HE） staining was conducted to analyze lung histopathology. Serum levels of interleukin-17A （IL-17A）, IL-10, chemokine C-C motif ligand 20 （CCL20）, C-C chemokine receptor type 6 （CCR6） and Jagged1 and Notch1 protein expression levels in lung tissues were detected.
    RESULTS Compared with the control group, the model group showed lower FEV 0.3, FVC and FEV 0.3/FVC ratio, higher white blood cell count （WBC）, neutrophil count （NEU）, lymphocyte （Ly） and monocyte （Mon） counts in BALF, higher inflammatory infiltration score in the upper lung lobe, higher serum levels of IL-17A, CCL20 and CCR6, lower IL-10 levels and higher Jagged1 and Notch1 protein expression （P＜0.05）. Compared with the model group, the L-pachymic acid and H-pachymic acid groups exhibited higher FEV 0.3, FVC and FEV 0.3/FVC ratio, lower WBC, NEU, Ly and Mon counts in BALF, lower inflammatory infiltration score in the upper lung lobe, lower serum levels of IL-17A, CCL20 and CCR6, higher IL-10 levels and lower Jagged1 and Notch1 protein expression （P＜0.05）. Compared with the H-pachymic acid group, the H-pachymic acid + Jagged1 group exhibited lower FEV 0.3, FVC and FEV 0.3/FVC, higher counts of WBC, NEU, Ly and Mon cells in BALF, higher inflammatory infiltration scores in the upper lung lobes, higher serum levels of IL-17A, CCL20 and CCR6, lower IL-10 levels and higher Jagged1 and Notch1 protein expression （P＜0.05）.
    CONCLUSION  Poric acid may alleviate inflammatory response in chronic bronchitis rats by inhibiting the Jagged1/Notch1 signaling pathway.

     

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