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增塑剂BBP加重过敏性哮喘的免疫毒性效应研究

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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.
Immunotoxic Effect of Plasticizer BBP in Aggravating Allergic Asthma
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.

butyl benzyl phthalateallergic asthmaendoplasmic reticulum stressTh17 pathwayTreg pathway

李崇尧、曹青、薛飞、龚樊欣、曹楠、李慧、靳艳艳、闫抗抗

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西北大学附属医院/西安市第三医院药剂科,西安 710018

西北大学医学院,西安 710069

邻苯二甲酸丁基苄酯 过敏性哮喘 内质网应激 Th17通路 Treg通路

2024

生态毒理学报
中国科学院生态环境研究中心

生态毒理学报

CSTPCD北大核心
影响因子:0.857
ISSN:1673-5897
年,卷(期):2024.19(6)