以往的研究表明，使大鼠接触二丁基邻苯二甲酸酯（简称DBP）可能对繁殖和神经发育产生毒性作用。然而，DBP接触对其他内分泌器官的影响仍然不清楚。本研究旨在评估DBP接触对雄性大鼠甲状腺的影响及相关机制。通过胃内给药将大鼠分别接受0（对照组）、50（低剂量）、250（中剂量）或500（高剂量）mg/kg体重的DBP，溶于1ml玉米油中，为期两周。结果显示，增殖和炎症反应的变化与对照组明显不同。体内的DBP主要被转化为单丁基邻苯二甲酸酯（MBP），是产生DBP暴露不良反应的活性形式。因此，在体外实验中，我们使用1mM浓度的MBP对甲状腺滤泡上皮细胞株（Nthy-ori 3-1）进行时间梯度处理。进一步的体外研究显示，MBP接触通过激活AKT/NF-κB/NLRP3信号通路上调肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）以及白细胞介素1β（IL-1β）。同时，我们发现Pellino2（Peli2）在促进NLRP3炎症小体的激活中起到关键作用。总而言之，本研究证实，DBP接触导致雄性大鼠甲状腺结构受损和甲状腺炎症，为DBP接触对内分泌器官的危害提供了新的视角。版权所有 © 2023 作者。Elsevier Inc. 发表。保留所有权利。

Previous studies exhibited reproductive and neurodevelopmental toxicity in rats exposed to Di-n-butyl phthalate (DBP). However, the effects of DBP exposure on the other endocrine organ are still unclear. This study aimed to assess the impact of DBP exposure on the thyroid of male rats and the associated mechanisms. Here, rats were respectively treated with DBP at 0 (control), 50 (low dose), 250 (medium dose), or 500 (high dose) mg/kg/day dissolved in 1 ml quantity of corn oil by intragastrical administration for two weeks. The results demonstrated that the proliferation and inflammatory response changes were significantly different compared to the control. In vivo DBP is mainly converted to mono-n-butyl phthalate (MBP), an active form producing untoward reactions of DBP exposure. Therefore, for in vitro experiments, we treated the thyroid follicular epithelial cell line (Nthy-ori 3-1) in a temporal gradient using 1 mM MBP. Further in vitro studies showed that MBP exposure upregulated tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), as well as interleukin-1β (IL-1β) by activating AKT/NF-κB/NLRP3 signaling. Meanwhile, we detected that Pellino2 (Peli2) played an essential role in promoting the activation of NLRP3 inflammasome. Briefly speaking, this study confirmed that DBP exposure caused impaired thyroid structure and thyroid inflammation in male rats, which offered new views into the harm of DBP exposure on the endocrine organ.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.