Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, 1#Yixueyuan Road, Chongqing, 400016, People's Republic of China.
Sci Rep. 2020 Sep 3;10(1):14625. doi: 10.1038/s41598-020-71517-6.
Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract. Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and belongs to environmental endocrine disruptors (EDCs). It can be entered the human body which is harmful to health. The relationship between DEHP and AR is still inconclusive. This study aims to investigate the effect of environmental pollutants DEHP on AR. By examining DEHP metabolites in the urine of AR patients and building an AR model. 24 BALB/c mice were used as the study subjects, and ovalbumin (OVA) and DEHP (3 mg/kg/body) were used for intragastric administration. They were divided into control group, DEHP group, OVA group and OVA + DEHP group. Examination, behavioral scoring, inflammatory factor testing, oxidative stress testing, detection of aryl hydrocarbon receptor (AhR) and signaling pathways CYP1A1 and CYP1B1 related proteins and mRNA. The concentrations of 3 metabolites of DEHP (MEHHP, MEOHP, and MEHP) in urine of AR patients were higher. And HE-staining showed that for the control group, many chronic inflammatory cell infiltration and nasal mucosal destruction were observed in the OVA + DEHP group and were more severe than the OVA group. Allergic symptom scores were obtained from sneezing, scratching, number of scratching, and nose flow. The scores of the OVA group and the OVA + DEHP group were higher than 7 points. Serum ELISA and nasal mucosal oxidative stress tests are more serious in the OVA + DEHP group. The expression of AhR protein and its mRNA was increased in the DEHP group, OVA group and OVA + DEHP group. The OVA + DEHP group was more significant in the OVA group and DEHP group. And the mRNAs of the AhR-related signaling pathways CYP1A1 and CYP1B1 were also more prominent in the OVA + DEHP group. DEHP may aggravate its inflammatory response through the AhR pathway closely related to the environment. When combined with OVA, DEHP can further aggravate the OVA-induced nasal inflammatory response and make the nasal cavity have undergone severe changes, and many inflammatory cells have infiltrated. DEHP has shown an adjuvant effect, and the AhR-related signaling pathways CYP1A1 and CYP1B1 may be critical.
变应性鼻炎(AR)是一种常见的上呼吸道慢性炎症性疾病。邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种广泛使用的增塑剂,属于环境内分泌干扰物(EDCs)。它可以进入人体,对健康有害。DEHP 与 AR 之间的关系仍不确定。本研究旨在探讨环境污染物 DEHP 对 AR 的影响。通过检测 AR 患者尿液中的 DEHP 代谢物并建立 AR 模型。将 24 只 BALB/c 小鼠作为研究对象,采用卵清蛋白(OVA)和 DEHP(3mg/kg/体重)进行灌胃。它们被分为对照组、DEHP 组、OVA 组和 OVA+DEHP 组。检查、行为评分、炎症因子检测、氧化应激检测、检测芳香烃受体(AhR)和信号通路 CYP1A1 和 CYP1B1 相关蛋白和 mRNA。AR 患者尿液中 DEHP 的 3 种代谢物(MEHHP、MEOHP 和 MEHP)浓度较高。HE 染色显示,对于对照组,OVA+DEHP 组有大量慢性炎症细胞浸润和鼻黏膜破坏,比 OVA 组更严重。过敏症状评分包括打喷嚏、抓挠、抓挠次数和鼻涕流量。OVA 组和 OVA+DEHP 组的评分均高于 7 分。OVA+DEHP 组的血清 ELISA 和鼻黏膜氧化应激试验更为严重。DEHP 组、OVA 组和 OVA+DEHP 组 AhR 蛋白及其 mRNA 的表达增加。OVA+DEHP 组在 OVA 组和 DEHP 组更为明显。并且 OVA+DEHP 组 AhR 相关信号通路 CYP1A1 和 CYP1B1 的 mRNAs 也更为突出。DEHP 可能通过与环境密切相关的 AhR 途径加重其炎症反应。当与 OVA 结合时,DEHP 可以进一步加重 OVA 诱导的鼻黏膜炎症反应,使鼻腔发生严重变化,大量炎症细胞浸润。DEHP 表现出佐剂作用,AhR 相关信号通路 CYP1A1 和 CYP1B1 可能是关键。