Acute pancreatitis during pregnancy (APIP) rarely occurs but may lead to preterm delivery and be associated with high fetal mortality. Macrophage migration inhibitory factor (MIF) participates in various inflammatory diseases as a pro-inflammatory cytokine. In this study, we aimed to explore the effects of (S, R)-3-(4-hydroxyphenyl)-4, 5dihydro-5-isoxazole acetic methyl ester (ISO-1), an inhibitor of MIF, on maternal thyroid injury associated with APIP and its potential mechanisms in a pregnant rat model. APIP model was induced by retrograde injection of sodium taurocholate. ISO-1 was injected intraperitoneally 30 min before model establishment. The severity of pancreatitis was assessed by levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL-6 of maternal serum as well as histopathological score. Thyroid injury was determined by free triiodothyronine (FT3), free tetraiodothyronine (FT4) and thyroid histopathological score. Levels of MIF in maternal serum and the expression of MIF, CD68, CD3 and intercellular cell adhesion molecule-1 (ICAM-1) as well as oxidative stress status in maternal thyroid tissues were detected. Ultrastructure of maternal thyroid tissues was observed by transmission electron microscope. Thyroid injuries occurred in APIP and the lesions were attenuated with the pretreatment of ISO-1. Moreover, ISO-1 reduced the expression of MIF, attenuated the activations of CD68, CD3, ICAM-1 while improved oxidative stress status in maternal thyroid. Our research suggested a protective role of ISO-1 on thyroid injury and endocrine disorder during APIP, which may be associated with the inhibition of biological functions of MIF.

怀孕期间急性胰腺炎（APIP）很少发生，但可能导致早产并与高胎儿死亡率相关。巨噬细胞迁移抑制因子（MIF）作为促炎细胞因子参与各种炎性疾病。在这项研究中，我们旨在探讨MIF抑制剂（S，R）-3-（4-羟苯基）-4，5dihydro-5-isoxazole乙酸甲酯（ISO-1）对孕妇甲状腺损伤的影响与APIP及其在妊娠大鼠模型中的潜在机制有关。逆行注射牛磺胆酸钠可诱发APIP模型。在建立模型前30分钟腹膜内注射ISO-1。通过肿瘤坏死因子（TNF）-α，白细胞介素（IL）-1β，母体血清IL-6的水平以及组织病理学评分来评估胰腺炎的严重程度。甲状腺损伤由游离三碘甲状腺素（FT3），游离四碘甲状腺素（FT4）和甲状腺组织病理学评分确定。检测母体血清中的MIF水平以及母体甲状腺组织中MIF，CD68，CD3和细胞间细胞粘附分子1（ICAM-1）的表达以及氧化应激状态。透射电镜观察母体甲状腺组织的超微结构。APIP发生甲状腺损伤，并且通过ISO-1预处理减轻了病变。此外，ISO-1降低了MIF的表达，减弱了CD68，CD3，ICAM-1的活化，同时改善了孕妇甲状腺的氧化应激状态。我们的研究表明ISO-1对APIP期间甲状腺损伤和内分泌失调具有保护作用，这可能与抑制MIF的生物学功能有关。