大蒜素抑制TGF-β1/SMAD2通路减轻哮喘小鼠气道炎症并调节气道重塑

Allicin inhibits TGF-β1/SMAD2 pathway to reduce airway inflammation and regulate airway remodeling in asthmatic mice

目的探究大蒜素对支气管哮喘小鼠气道炎症和气道重塑的作用机制。方法随机选取健康雌性BALB/c小鼠,分对照组、哮喘模型组和大蒜素处理组,每组8只。采用卵清蛋白(OVA)致敏和激发建立小鼠哮喘模型,取小鼠支气管肺泡灌洗液进行炎细胞计数,HE染色观察肺组织病理学变化、Masson染色观察肺气道重塑情况,免疫组织化学染色法检测肺组织α平滑肌肌动蛋白(α-SMA)的表达,ELISA检测小鼠血清白细胞介素4(IL-4)、γ干扰素(IFN-γ)的水平,Western blot法检测小鼠肺组织中转化生长因子β1(TGF-β1)和SMAD家族成员2(SMAD2)、SMAD7的表达水平。结果与哮喘模型组比,大蒜素能显著抑制哮喘小鼠肺泡灌洗液中炎性细胞数量的增加并减轻炎性细胞的浸润、平滑肌增生及胶原蛋白沉积。同时,大蒜素能降低血清中IL-4的水平,升高IFN-γ的水平,抑制肺组织中TGF-β1、SMAD2、α-SMA蛋白表达,增加SMAD7蛋白表达。结论大蒜素可通过抑制TGF-β1/SMAD2通路减轻哮喘小鼠气道炎症并调节气道重塑。

Objective To investigate the impact of allicin on airway inflammation and airway remodeling in mice with asthma and related mechanism.Methods Healthy female BALB/c mice were randomly divided into control group,model group and allicin treatment group,with 10 mice in each.The mouse asthma model was established by sensitization and challenge of ovalbumin(OVA).The bronchoalveolar lavage fluid(BALF)of mice was taken for inflammatory cell count;HE staining was used to observe the pathological changes of lung tissue;Masson staining was used to observe the airway remodeling;immunohistochemical staining was performed to detect the expression ofαsmooth muscle actin(α-SMA)in the lung tissue;ELISA was conducted to assess the levels of serum interleukin-4(IL-4)and interferon-γ(IFN-γ);Western blotting was used to detect the expression of transforming growth factor-β1(TGF-β1),SMAD2 and SMAD7 in the lung tissue.ResultsCompared with the asthma model group,allicin significantly inhibited the increase of inflammatory cell number in the BALF and reduced the infiltration of inflammatory cells,smooth muscle proliferation and collagen deposition.Meanwhile,allicin decreased the level of IL-4 in serum,increased the level of IFN-γ,inhibited the expression of TGF-β1,SMAD2 andα-SMA in the lung tissue,and increased the expression of SMAD7.Conclusion Allicin can reduce airway inflammation and regulate airway remodeling in asthmatic mice by inhibiting the TGF-β1/SMAD2 signaling pathway.