葫芦素E通过抑制MAPKs/NF-κB通路减轻哮喘小鼠气道炎症

Cucurbitin E relieves airway inflammation by inhibiting MAPKs/NF-κB signaling pathways in asthmatic mice

目的:探讨葫芦素E对哮喘小鼠气道炎症及MAPKs和NF-κB信号通路的影响。方法:将40只健康小鼠随机分成对照组、模型组、葫芦素E低剂量组、葫芦素E高剂量组和地塞米松组。用卵清蛋白致敏法制备哮喘模型,观察各组支气管肺泡灌洗液(BALF)中炎症细胞分类计数、肺组织炎症细胞浸润以及BALF中白细胞介素4(IL-4)、IL-5、IL-13及干扰素γ(IFN-γ)含量的变化;测定肺组织中磷酸化JNK(p-JNK)、磷酸化ERK1/2(p-ERK1/2)、磷酸化p38 MAPK(p-p38 MAPK)和磷酸化NF-κB p65(p-p65)的含量。结果:与正常组比,模型组BALF中炎症细胞数量明显增加,并且MAPKs和NF-κB信号通路相关蛋白活性显著增强。我们发现高剂量葫芦素E可减轻哮喘小鼠气道炎症反应,并明显抑制MAPKs和NF-κB信号通路相关蛋白活性。病理组织学结果显示,模型组小鼠肺组织内有杯状细胞及支气管黏膜上皮细胞增生,肺泡内有炎症细胞浸润,管腔狭窄;各剂量葫芦素E处理组病理改变均较模型组显著减轻。结论:葫芦素E可以减轻哮喘小鼠气道炎症反应,其机制可能与抑制MAPKs和NF-κB信号通路有关。

AIM:To investigate the effects of cucurbitacin E on airway inflammation and the signaling pathways of MAPKs and NF-κB in asthmatic mice.METHODS:Healthy mice(n=40)were randomly divided into control group,model group,low-dose cucurbitacin E group,high-dose cucurbitacin E group and dexamethasone group. Ovalbumin sensitization was used to induce asthma in the mice. The protein levels of p-JNK,p-ERK1/2,p-p38 MAPK and p-p65 in the lung tissues were determined by Western blot.RESULTS:Compared with control group,the numbers of inflammatory cells,such as eosinophils,lymphocytes and neutrophils,were significantly increased in model group,and the activity of MAPKs and NF-κB signaling pathway-related proteins was significantly enhanced. Cucurbitin E at high dose attenuated airway inflammation in asthmatic mice,and significantly inhibited the activity of MAPKs and NF-κB signaling pathway-related proteins. Histopathological results showed proliferation of goblet cells and bronchial mucosal epithelial cells,infiltration of inflammatory cells in the alveoli,and narrow alveolar cavity in model group,while the pathological changes were significantly alleviated in cucurbitin E treatment groups.CONCLUSION:Cucurbitin E improves airway inflammation in asthmatic mice,and its mechanism may be related to the inhibition of MAPKs and NF-κB signaling pathways.