摘要
为了研究增塑剂邻苯二甲酸丁基苄酯(BBP)加重过敏性哮喘的作用机制,采用雄性BALB/c小鼠,并随机分组,造模周期为37 d.具体分5组:生理盐水组、卵清蛋白(OVA)组、10 mg·kg-1 BBP+OVA组、100 mg·kg-1 BBP+OVA组和250 mg·kg-1 BBP+OVA组.主要检测总免疫球蛋白E(T-IgE)、OVA特异性免疫球蛋白E(OVA-IgE)、白细胞介素-17(IL-17)和白细胞介素-22(IL-22);分析肺组织免疫组化切片内质网应激标志物激活转录因子6(ATF6)和C/BEP同源蛋白(CHOP)、Treg通路分子白细胞介素-10(IL-10)和叉头框蛋白P3(FoxP3);观察肺组织切片改变程度,并同时用无创呼吸机评估肺功能指标.结果表明,与生理盐水组比较,OVA组的T-IgE、OVA-IgE功能、肺功能和病理学损伤均有所加重,辅助T型17细胞/调节性T细胞(Th17/Treg)平衡被破坏.与OVA组比较,不同浓度BBP+OVA组随着BBP浓度的升高,其肺功能、T-IgE、OVA-IgE功能和病理学损伤均逐渐加重,平衡向Th17进行,在100 mg,kg-1组出现显著性差异.研究表明BBP可以通过内质网应激调节Th17/Treg通路,从而加重过敏性哮喘,BBP剂量为100 mg,kg-1时有显著性差异.
Abstract
The aim of this study is to investigate the mechanism of the plasticizer butyl benzyl phthalate(BBP)in exacerbating allergic asthma.This study included male BALB/c mice,which were randomly divided into the fol-lowing five groups,with a modeling period of 37 days:(1)physiological saline group,(2)ovalbumin(OVA)group,(3)10 mg·kg-1 BBP+OVA group,(4)100 mg·kg-1 BBP+OVA group,and(5)250 mg·kg-1 BBP+OVA group.The study primarily assessed total immunoglobulin E(T-IgE),OVA-specific immunoglobulin E(OVA-IgE),interleukin-17,and interleukin-22.Additionally,endoplasmic reticulum stress markers activating transcrip-tion factor-6(ATF6)and C/BEP homologous protein(CHOP),T regulatory(Treg)pathway molecules interleu-kin-10,and forkhead box protein P3 in immunohistochemical sections of lung tissue were analyzed.Lung func-tion was evaluated by observing lung tissue changes and using a noninvasive ventilator.The results showed that compared with the saline group,the T-IgE,OVA-IgE function,lung function,and pathological damage in the OVA group were all aggravated,while the Th17/Treg balance was disrupted.Compared with the OVA group,as the concentration of BBP increased,the lung function,T-IgE,OVA-IgE function,and pathological damage in the different concentrations of BBP+OVA groups progressively worsened,shifting the balance toward Th17,with significant differences at 100 mg·kg-1.Furthermore,the experimental results revealed that BBP exacerbates aller-gic asthma by regulating the Thl7/Treg pathway through endoplasmic reticulum stress,with a significant effect noted at a BBP dose of 100 mg·kg-1.
维普
万方数据