Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, 130021, China.
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, 130021, China.
Food Chem Toxicol. 2024 May;187:114609. doi: 10.1016/j.fct.2024.114609. Epub 2024 Mar 22.
DEHP has thyroid toxicity and affects thyroid function. However, the mechanism is unclear.
The offspring of SD rats were gavaged with different doses of DEHP from in utero to 8 or 12 weeks old. We observed the thyroid morphology with HE and autophagosomes with TEM. The THs levels were tested with ELISA. The apoptosis level was tested by flow cytometry. The levels of apoptosis-related genes, autophagy-related genes and Rap1 pathway genes, were measured with qRT-PCR and Western blot. We established an MEHP-treated Nthy-ori 3-1 cell model and inhibited the Rap1 to verify the mechanism.
DEHP could cause pathological damage and ultrastructure damage of thyroids in offspring rats. After DEHP exposure, the THs levels were altered, the apoptosis levels increased, and autophagosomes appeared. DEHP significantly affected the levels of apoptosis-related genes and autophagy-related genes. DEHP also affected the levels of Rap1 pathway, which was correlated with the levels of apoptosis and autophagy. After inhibiting Rap1 in Nthy-ori 3-1 cells, the THs levels were altered. Rap1 pathway was inhibited and the levels of apoptosis and autophagy were down-regulated.
DEHP could induce the apoptosis and autophagy of the thyroid, and Rap1 signaling pathway may play a significant role.
DEHP 具有甲状腺毒性，会影响甲状腺功能。然而，其具体机制尚不清楚。
SD 大鼠仔鼠从宫内到 8 或 12 周龄时给予不同剂量的 DEHP 灌胃。我们用 HE 观察甲状腺形态，用 TEM 观察自噬体。用 ELISA 法检测甲状腺激素（THs）水平。用流式细胞术检测细胞凋亡水平。用 qRT-PCR 和 Western blot 法测定凋亡相关基因、自噬相关基因和 Rap1 通路基因的水平。建立 MEHP 处理的 Nthy-ori 3-1 细胞模型，抑制 Rap1，验证其作用机制。
DEHP 可导致仔鼠甲状腺发生病理损伤和超微结构损伤。DEHP 暴露后，THs 水平改变，细胞凋亡水平升高，自噬体出现。DEHP 还显著影响凋亡相关基因和自噬相关基因的水平。DEHP 还影响 Rap1 通路的水平，与细胞凋亡和自噬的水平相关。在 Nthy-ori 3-1 细胞中抑制 Rap1 后，THs 水平发生改变。Rap1 通路被抑制，细胞凋亡和自噬水平下调。
DEHP 可诱导甲状腺细胞凋亡和自噬，Rap1 信号通路可能发挥重要作用。
