阿里红调控MAPK/NF-κB信号通路对过敏性哮喘小鼠的影响及作用机制

Effect of Fomes of ficinalis on regulating MAPK/NF-κB signaling pathway on allergic asthma in mice and its mechanism

目的:探讨阿里红多糖(FOPS)和阿里红醇提物(FOEE)对卵清白蛋白(OVA)诱导的过敏性哮喘小鼠模型的干预作用及潜在机制。方法:将72只雌性BALB/c小鼠随机分成9组,每组8只,分为正常组(Control),OVA诱导的过敏性哮喘模型组(OVA),阳性对照组(桂龙咳喘宁,Guilong),FOPS低、中、高剂量组(50,100,200 mg·kg^(-1)),FOEE低、中、高剂量组(50,100,200 mg·kg^(-1))。观察并比较小鼠体质量变化、肺组织病理学变化;测定各组小鼠支气管肺泡灌洗液(BALF)中炎症细胞数量、IL-4、IL-5及TNF-α的含量;测定各组小鼠肺组织中磷酸化p38 MAPK(p-p38 MAPK)和磷酸化NF-κB p65(p-NF-κB p65)蛋白表达。结果:模型组小鼠BALF中炎症总细胞数量、嗜酸性粒细胞、中性粒细胞、淋巴细胞和单核细胞的数量,BALF中IL-4、IL-5和TNF-α的含量,肺组织p-p38 MAPK、Caspase-1、p-IκBα和p-NF-κB p65蛋白表达均明显高于正常组(P<0.01),FOPS组,FOEE组和Guilong组上述指标则明显低于模型组(P<0.05或P<0.01)。结论:FOPS与FOEE均对小鼠过敏性哮喘具有改善作用,且FOPS的作用强于FOEE,其作用机制可能为通过干预MAPK/NF-κB信号通路从而改善OVA诱导的哮喘小鼠气道炎症。

OBJECTIVE To investigate the effects of Fomes of ficinalis FOPS and FOEE on OVA-sensitized allergic asthma model in mouse.METHODS Seventy-two female BALB/c mice were randomly divided into eight groups in normal group(Control),OVA-induced allergic asthma model(OVA),Guilong-positive control(Guilong),50,100 and 200 mg·kg^(-1)doses(FOPS-L,FOPS-M,FOPS-H),and alcohol extract 50,100 and 200 mg·kg^(-1)(FOEE-L,FOEE-M,FOEE-H).The mouse model of allergic asthma was established by OVA combined with aluminum hydroxide sensitization method,observed and recorded the mouse body mass changes and the general situation,detected the lung histopathological changes,and observed the number of inflammatory cells in bronchoalveolar lavage fluid(BALF)and the changes of IL-4,IL-5 and TNF-αcontent in BALF in each group;Phosphorylated p38 MAPK(p-p38 MAPK)and phosphorylated NF-κB p65(p-NF-κBp65)were determined in the lung tissue.RESULTS The total number of inflammatory cells,the number of eosinophils,neutrophils,lymphocytes and monocytes,the content of IL-4,IL-5 and TNF-αin BALF,and the expression of p-p38 MAPK,Caspase-1,p-IκBαand p-NF-κB p65 proteins in the model group were significantly higher than those in the normal group(P<0.01).All of these parameters were reversed by the treatment of FOPS,FOEE and Guilong group(P<0.05 or P<0.01).CONCLUSION FOPS and FOEE both have an improving effect on allergic asthma in mice,and the effect of FOPS is slightly stronger than that of FOEE,and its mechanism of action may improve OVA-induced airway inflammation in asthmatic mice by intervening in the MAPK/NF-κB signaling pathway.