木犀草素对哮喘小鼠气道重塑的影响及机制探讨

Effects of luteolin on airway remodeling in asthmatic mice

目的观察中药木犀草素对哮喘小鼠气道重塑的抑制作用并探讨其可能机制。方法32只BALB/c小鼠随机分为正常对照组、哮喘组、地塞米松组、木犀草素组,鸡卵蛋白致敏反复雾化吸入共8周,建立哮喘气道重塑模型,并分别使用地塞米松(2mg.kg-1)及木犀草素(1 mg.kg-1)进行干预。观察支气管肺泡灌洗液(BALF)中白细胞介素-5(IL-5)和γ干扰素(IFN-γ)水平的变化。对肺组织切片行苏木精-伊红(HE)染色,借助图像分析软件测量单位气道基底膜周径(Pbm,μm)、平滑肌面积(WAm,μm2)、管壁面积(WAt,μm2),计算出支气管管壁厚度(WAt/Pbm,μm2/μm)和平滑肌厚度(WAm/Pbm,μm2/μm)。结果经过反复抗原激发,哮喘组BALF中IL-5水平(50.7±2.9)μg.L-1明显高于正常对照组(16.1±1.2)μg.L-1、地塞米松组(26.8±1.5)μg.L-1和木犀草素组(25.9±2.6)μg.L-1(P均<0.05),IFN-γ水平(38.1±3.3)μg.L-1明显低于正常对照组(64.2±3.5)μg.L-1、地塞米松组(58.2±4.2)μg.L-1和木犀草素组(54.3±2.4)μg.L-1(P均<0.05),哮喘组支气管管壁厚度(WAt/Pbm)(17.1±1.6)μm2/μm和平滑肌厚度(WAm/Pbm)(6.0±0.5)μm2/μm明显高于正常对照组[(12.7±1.1)μm2/μm,(4.5±0.4)μm2/μm]、地塞米松组[(14.3±1.1)μm2/μm,(5.0±0.5)μm2/μm]和木犀草素组[(14.0±1.2)μm2/μm,(5.2±0.6)μm2/μm](P均<0.05),结果表明:木犀草素有显著的抗气道重塑作用。结论木犀草素可抑制气道壁的增厚和平滑肌增殖,减轻气道重塑,其作用的机制可能是通过减少IL-5的分泌,增加IFN-γ的分泌来实现。

Aim Our aim was to observe the effectiveness and mechanism of luteolin on the airway remodeling in asthmatic mice. Methods Thirty-two BALB/c mice were randomly divided into four groups - control group （ group A）, asthma group （ group B）, dexamethasone （DXM） treated group （ group C） and luteolin treated group （ group D）. The asthma group, DXM treated group and luteolin treated group were sensitized and repeatedly challenged with OVA for eight weeks and were treated with normal saline （ 10 ml·kg^-1 ） , DXM （2 mg· kg^-1） and luteolin （1 mg ·kg^-1）, respectively. To observe the levels of interleukin-5 （IL-5） and interferon gamma（IFN-γ） in the bronchoalveolar lavage fluid（BALF）. The morphological parameters including bronchial basement membrane perimeter（ Pbm, μm） , smooth muscle area（ WAm, μm^2 ）, bronchial wall area（ WAt, μm^2 ） were measured by image analysis software, then the airway smooth muscle thickness（WAm/Pbm,μm2/μm） and the airway wall thickness（WAt/Pbm,μm^2/μm） were figured out. Results The IL-5 level in BALF of group B [ （ 50.7 ± 2.9 ） μg · L^-1 ] increased significantly and the IFN-γ,level [ （ 38.1 ± 3.3 ） μg ·L^-1] decreased significantly compared with groupA[（16.1 ±1.2） μg·L^-1, （64.2±3.5） μg·L^-1], groupC[（26.8±1.5） μg· L^-1,（58.2±4.2） μg·L^-1 ] and group D [ （ 25.9 ± 2.6 ） μg·L^-1, （ 54.3 ± 2.4 ） μg · L^-1 ] respectively （ all P 〈 0.05 ）. The airway wall thickness （WAt/Pbm） and the airway smooth muscle thickness（WAm/Pbm） in group B [ （17.1 ± 1.6 ）μm^2/μm, （6.0 ± 0.5 ）μm^2/μm ] were significantly greater than those in group A[ （ 12.7± 1.1 ） μm^2/μm, （4.5 ± 0.4）μm^2/μm], group C [ （ 14.3 ± 1.1 ） μm^2/μm, （ 5.0 ± 0. 5 ） μm^2/μm ] and group D [ （ 14.0 ± 1.2 ） μm^2/μm, （ 5.2± 0.6 ）μm^2/μm ] （ all P 〈 0.05 ）. The results indicate that luteolin has a noticeable anti-airway remodeling activity. Conclusion Luteolin might inhibit the thickness increasing of airway wall and airway smooth muscle proliferation , then inhibit airway remodeling. Its possible mechanisms are to by the way of decreasing the levels of IL-5 and increasing the levels of IFN-γ in the lung tissue.