基于IL-13/STAT6信号通路研究祛风宣痹方对哮喘气道黏液高分泌的影响

目的：探讨祛风宣痹方对哮喘小鼠气道黏液分泌及IL-13/STAT6信号通路的影响。方法：采用卵清蛋白（OVA）致敏建立小鼠哮喘模型。将24只Balb/c雌性小鼠随机分为对照组、哮喘组、祛风宣痹方组，祛风宣痹方组给予祛风宣痹方治疗，对照组和哮喘组给予等量生理盐水灌胃。采用肺组织HE染色、PAS染色观察肺组织病理形态变化以及气道黏液分泌，免疫组化实验观察黏蛋白MUC5AC、p-STAT6蛋白表达情况，ELISA实验检测小鼠血清中IL-13的含量。IL-13处理A549细胞模拟黏蛋白分泌病理模型（IL-13组），再加入祛风宣痹方进行干预（IL-13+祛风宣痹方组）；采用免疫荧光技术检测A549细胞中MUC5AC和p-STAT6的表达情况。结果：体内实验发现，与哮喘组相比，祛风宣痹方组小鼠肺组织中炎症细胞浸润及黏液高分泌情况均有明显改善，气道表面细胞MUC5AC、p-STAT6蛋白表达有所降低（P < 0.05）；小鼠血清中IL-13含量也明显减少（P < 0.01）。体外实验发现，与对照组相比，IL-13组A549细胞中MUC5AC及p-STAT6蛋白表达明显升高（P < 0.01），而IL-13+祛风宣痹方组细胞中MUC5AC及p-STAT6蛋白表达相对于IL-13组呈现明显下降趋势（P < 0.05）。结论：祛风宣痹方可减轻哮喘气道黏液高分泌，其作用机制可能与抑制IL-13/STAT6信号通路相关。

Effects of QufengXuanbi Formula on the Hypersecretion of Airway Mucus in Asthma Based on the IL-13/STAT6 Signaling Pathway*

Objective: To explore the effects of QufengXuanbi Formula (QFXBF) on airway mucus secretion and IL-13/STAT6 signal pathway in asthmatic mice. Methods: Ovalbumin (OVA) sensitization was used to establish a mouse asthma model. Twenty-four female Balb/c mice were randomly divided into control group, asthma group and QFXBF group. Mice in the QufengXuanbi Formula group were treated with QufengXuanbi Formula by gavage, and those in the control and asthma groups were treated with the same amount of normal saline. Hematoxylin and eosin (H&E) staining and periodic acid-schiff staining were used to observe the pathological morphological changes and airway mucus secretion, immunohistochemistry was used to observe the expression of MUC5AC and P-STAT6 proteins, and ELISA was used to detect the contents of IL-13 in mouse serum. A549 cells were treated with IL-13 to form a pathological model mimicking mucin secretion (IL-13 group), and the QufengXuanbi Formula were added for intervention (IL-13 + QFXBF group). The expression of MUC5AC and P-STAT6 in the A549 cells were detected by immunofluorescence. Results: In vivo experiments showed that compared with the asthma group, the inflammatory cell infiltration and mucus hypersecretion in lung tissues of mice in the QufengXuanbi Formula group were significantly improved, the expression of MUC5AC and P-STAT6 proteins in airway surface cells were reduced (P < 0.05), and the contents of IL-13 in mouse serum were significantly reduced (P < 0.01). The results of A549 cell experiments showed that compared with the control group, the expression of MUC5AC and P-STAT6 proteins in the IL-13 group were significantly increased (P < 0.01), while the expression of MUC5AC and P-STAT6 proteins showed a significant downward trend in the IL-13 + QufengXuanbi Formula group compared with those in the IL-13 group (P < 0.05). Conclusion: The QufengXuanbi Formula can significantly improve the airway mucus hypersecretion in asthma, and its mechanism of action may be related to the inhibition of IL-13/STAT6 signaling pathway.