姜黄素通过IL-13/STAT6信号通路抑制哮喘大鼠气道黏液高分泌

Curcumin improves airway inflammation and mucus hypersecretion by inhibiting IL-13/STAT6 signaling pathway in asthmatic rats

目的 探讨姜黄素通过白介素13 （IL-13）信号通路调控哮喘大鼠气道炎症、气道杯状细胞化生和黏液分泌的作用。方法 将24只雌性清洁级SD大鼠随机分为阴性对照组、哮喘模型组、姜黄素组和地塞米松组,每组6只。采用卵蛋白致敏和激发建立哮喘大鼠模型,阴性对照组给予生理盐水,通过 HE染色及高碘酸-无色品红法染色观察大鼠肺组织的病理学改变及气道上皮杯状细胞的数量,采用酶联免疫吸附试验法测定大鼠肺泡灌洗液中 MUC5AC黏蛋白和IL-13的含量,免疫组织化学法检测大鼠气道上皮中 MUC5AC的表达。蛋白质印迹法分析大鼠肺组织中磷酸化信号转导与转录激活因子6 （p-STAT6）的表达水平。结果 与阴性对照组相比,哮喘模型组大鼠肺组织可见大量炎性细胞浸润,杯状细胞数量明显增加,支气管肺泡灌洗液 （BALF）中嗜酸粒细胞比例、MUC5AC及IL-13水平明显升高 （P ＆lt;0 05）,肺组织p-STAT6的表达明显增加 （P ＆lt;0 05）。与哮喘模型组相比,姜黄素组大鼠气道炎症和杯状细胞化生程度明显减轻,BALF中嗜酸粒细胞比例、MUC5AC及IL-13水平明显降低 （P ＆lt;0 05）,肺组织p-STAT6的表达明显减少 （P ＆lt;0 05）,与地塞米松组相比,差异无统计学意义 （P ＆gt;0 05）。结论 姜黄素可以抑制哮喘大鼠的气道炎症及杯状细胞化生,减少气道黏蛋白 MUC5AC的表达,其作用机制可能是通过抑制IL-13/STAT6信号通路的活性而实现的。

Objective To explore the effects of curcumin on airway inflammation, airway goblet cells metaplasia and mucus secretion through interleukin-13 （IL-13）/signal transducers activator of transcription 6 （STAT6） signaling pathway in asthmatic rats. Methods Twenty-four female SD rats were randomly divided into four groups： negative control group, asthma model group, eurcumin group and dexamethasone group （ n = 6）. For asthma model establishing, the rats were sensitized and challenged with ovalbumin, while the negative controls received saline. The lung tissue sections were stained with hematoxylin-eosin staining for histopathological examinationand the number of airway epithelium goblet cells were examined with periodic acid-schiff stain. The concentration of MUCSAC and IL-13 in bronchoalveolar lavage fluid （BALF） was measured by enzyme linked immunosorbent assay, and the expression of MUCSAC in airway epithelial ceils were demonstrated by immunohis to chemistry. The p- STAT6 protein expression were detected by Western Blot. Results Compared with the negative control group, the infiltration of inflammatory cells was observed in the lung tissue of the asthma model group, the number of goblet cells was significantly increased, the proportion of eosinophils, the concentration of MUC5AC and IL-13 in BALF were significantly increased （ P〈0.05）. The expression of p-STAT6 in lung tissue was also significantly increased （ P〈0.05）. Compared with asthma model group, the airway inflammation and goblet cells were significantly reduced in curcumin group, and the levels of eosinophils, MUC5AC, IL-13 and p-STAT6 were significantly decreased （P〈0.05）. There was no significant difference between the curcumin group and the dexamethasone group （P〉 0.05 ）. Conclusions Curcumin can inhibit the metaplasia of airway epithelial goblet cells and decrease the expression of MUC5AC in airway epithelium of asthmatic rats. The mechanism of curcumin may be achieved by inhibiting the activity of IL-13/STAT6 signaling pathway.