欧前胡素通过p38MAPK/NF-κB途径改善哮喘小鼠气道炎症

Imperatorin reduces airway inflammation in asthmatic mice through p38MAPK/NF-κB pathway

目的探究欧前胡素对哮喘小鼠气道炎症的影响,其机制是否与p38MAPK/NF-κB信号通路有关。方法将50只雌性Balb/c小鼠进行随机分组并建立OVA诱导的小鼠哮喘模型,分别用30 mg/kg和10 mg/kg欧前胡素及0.5 mg/kg地塞米松治疗,对照组用生理盐水代替。末次激发24 h后处死小鼠,取肺泡灌洗液及肺组织备用。行HE、PAS、Masson染色观察小鼠肺组织病理学变化;Diff-Quick染色对小鼠BALF中的细胞进行分类和计数;ELISA法检测小鼠BALF中IL-4、IL-5、IL-13和IFN-γ的含量;免疫组织化学染色观察p-p38MAPK及NF-κBp65的表达量;Western blot对肺组织中p-p38MAPK及NF-κBp65的含量进行定量分析。结果欧前胡素能显著抑制小鼠肺组织中的炎性细胞浸润、黏液分泌和杯状细胞的增生以及胶原沉积;减少BALF中炎症细胞数量,并降低小鼠BALF中IL-4、IL-5、IL-13的含量同时增加IFN-γ含量;欧前胡素也能抑制p38MAPK的磷酸化,进而抑制NF-κB的表达和活化。结论欧前胡素能抑制哮喘小鼠的气道炎症,其机制可能与p38MAPK/NF-κB信号传导通路有关。

Imperatorin（IPT） is an active natural furocoumarin with various pharmacological effects, including anti-inflammatory, analgesic, anti-spasm, anti-cancer and so on. The purpose of this study was to evaluate the effects of IPT in reducing airway inflammation in（OVA）-induced asthmatic mice models and to explore its possible molecular mechanisms. Fifty female Balb/c mice were randomly divided into groups and established OVA-induced asthma mice models. 30 mg/kg and 10 mg/kg imperatorin and 0.5 mg/kg dexamethasone were used for treatment and normal saline was used in the control group instead. The mice were sacrificed 24 h after the last challenge, and bronchoalveolar lavage fluid and lung tissue were taken as backup. HE, PAS and Masson staining were used to observe the pathological changes of lung tissue in mice; Diff-Quick staining was used to classify and count the cells in BALF; ELISA was used to detect the content of IL-4, IL-5, IL-13 and IFN-γ in BALF of mice. The content of pp38 MAPK and NF-κBp65 were detected by immunohistochemical staining. Western blotting was used to quantitatively analyze the content of p-p38 MAPK and NF-κBp65 in lung tissue. The results showed that imperatorin can significantly inhibit infiltration of inflammatory cells, mucus secretion and goblet cell hyperplasia and collagen deposition in mice lung tissue; and reduce the number of inflammatory cells in BALF and decrease the content of IL-4, IL-5 and IL-13 in BALF, and at the same time increased the content of IFN-γ. Imperatorin can also inhibit the phosphorylation of p38 MAPK, thereby inhibiting the expression and activation of NF-κB. The above results indicate that imperatorin can inhibit asthmatic airway inflammation, and its mechanism may be related to p38 MAPK/NF-κB signaling pathway.