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目的 探究麻黄碱对支气管哮喘小鼠气道重塑的影响及对转化生长因子β1(TGF-β1)/Smads通路的调控作用。方法 将所有小鼠随机分为对照组、模型组、地塞米松组、麻黄碱低剂量组、麻黄碱高剂量组、麻黄碱高+TGF-β1激活剂组，每组12只。除对照组，其余组小鼠腹腔注射含有40μg卵清蛋白(OVA)和2 mg 10%氢氧化铝的致敏液诱导哮喘模型。8周后，检测各组小鼠气道高反应性；对支气管肺泡灌洗液(BALF)中嗜酸性粒细胞进行计数；ELISA检测BALF中白细胞介素(IL)-4、IL-5和IL-13的水平；苏木精-伊红(HE)染色和Masson染色观察小鼠肺组织的病理学变化及胶原纤维面积；免疫组织化学检测小鼠肺组织中α-平滑肌肌动蛋白(α-SMA)表达；Western blot检测小鼠肺组织中TGF-β1/Smads通路相关蛋白的表达。结果 与对照组相比，模型组小鼠不同乙酰甲胆碱剂量下的气道高反应性、气道壁的总面积(Wat)/基底膜的周长(Pbm)比值、胶原纤维面积、嗜酸性粒细胞及IL-4、IL-5、IL-13含量、α-SMA、TGF-β1表达及p-Smad2/Smad2、p-Smad3/Smad3比值均升高(P<0.05),Smad7表达降低(P<0.05);与模型组相比，地塞米松组和麻黄碱低、高剂量组小鼠不同乙酰甲胆碱剂量下的气道高反应性、Wat/Pbm比值、胶原纤维面积、嗜酸性粒细胞及IL-4、IL-5、IL-13含量、α-SMA、TGF-β1表达及p-Smad2/Smad2、p-Smad3/Smad3比值均降低(P<0.05),Smad7表达升高(P<0.05);与麻黄碱高剂量组相比，麻黄碱高+TGF-β1激活剂组小鼠不同乙酰甲胆碱剂量下的气道高反应性、Wat/Pbm比值、胶原纤维面积、嗜酸性粒细胞及IL-4、IL-5、IL-13含量、α-SMA、TGF-β1表达及p-Smad2/Smad2、pSmad3/Smad3比值均升高(P<0.05),Smad7表达降低(P<0.05)。结论 麻黄碱可以改善支气管哮喘小鼠的气道重塑，其机制与调控TGF-β1/Smads信号通路有关。
Abstract：Objective To explore the effect of ephedrine on airway remodeling and its regulation effect on transforming growth factor-β1(TGF-β1)/Smads pathway in asthmatic mice. Methods All mice were randomly separated into control group, model group, dexamethasone group, ephedrine low-dose group, ephedrine high-dose group, and ephedrine high-dose+TGF-β1 activator group, with 12 mice in each group. Except for the control group, mice in other groups were intraperitoneally injected with 40 μg ovalbumin(OVA) and 2 mg 10% aluminium hydroxide sensitizer to induce asthma models. After 8 weeks, the airway hyperresponsiveness of mice in each group was detected; eosinophils in bronchoalveolar lavage fluid(BALF) were counted; ELISA was applied to detect the levels of interleukin(IL)-4, IL-5, and IL-13 in BALF; hematoxylin-eosin(HE) staining and Masson staining were applied to observe the pathological changes and collagen fiber area of mouse lung tissue; immunohistochemistry was applied to detect the expression of α-smooth muscle actin(α-SMA) protein in mouse lung tissue; Western blot was applied to detect the expression of TGF-β1/Smads pathway related proteins in mouse lung tissue. Results Compared with the control group, the airway hyperreactivity at different doses of methacholine, total area of airway wall(Wat)/perimeter of the basement membrane(Pbm) ratio, collagen fiber area, eosinophil, the contents of IL-4, IL-5, IL-13, the expression of α-SMA, TGF-β1, the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the model group increased(P<0.05), the expression of Smad7 decreased(P<0.05); compared with the model group, the airway hyperreactivity at different doses of methacholine, Wat/Pbm ratio, collagen fiber area, eosinophil, the contents of IL-4, IL-5, IL-13, the expression of α-SMA, TGF-β1, the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the dexamethasone group, the ephedrine low-dose and high-dose groups decreased(P<0.05), the expression of Smad7 increased(P<0.05); compared with the ephedrine high-dose group, the airway hyperreactivity at different doses of methacholine, Wat/Pbm ratio, collagen fiber area, eosinophil, the contents of IL-4, IL-5, IL-13, the expression of α-SMA, TGF-β1, the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the ephedrine high-dose+TGF-β1 activator group increased(P<0.05), the expression of Smad7 decreased(P<0.05). Conclusion Ephedrine can improve airway remodeling in asthmatic mice, and its mechanism is related to the regulation of TGF-β1/Smads signaling pathway.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2024.08.016
中图分类号:R285.5
引用信息:
[1]范慧慧,任玉梅,田新磊等.麻黄碱调控TGF-β1/Smads通路对支气管哮喘小鼠气道重塑的影响[J].安徽医科大学学报,2024,59(08):1398-1404.DOI:10.19405/j.cnki.issn1000-1492.2024.08.016.
基金信息:
河南省中医药科学研究专项(编号：20-21ZY2057)