长期共暴露于邻苯二甲酸二丁酯(DBP)和苯并[a]芘(BaP)通过 miR-34a-5p 调控的 Notch 信号通路激活导致大鼠肝巨噬细胞极化失衡。
Long-term co-exposure DBP and BaP causes imbalance in liver macrophages polarization via activation of Notch signaling regulated by miR-34a-5p in rats.
机构信息
School of Public Heath, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, 550025, China.
School of Public Heath, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, 550025, China.
出版信息
Chem Biol Interact. 2022 May 25;359:109919. doi: 10.1016/j.cbi.2022.109919. Epub 2022 Apr 2.
Humans are often exposed to complex mixtures of environmental pollutants over long periods of time. It is reported that Dibutyl phthalate (DBP) and benzo[a]pyrene (BaP) are typical environmental pollutants, which are associated with liver injury. Nevertheless, little is known about the effects of DBP and BaP combined exposure on liver. In the current study, rats were exposed to DBP alone (50, or 250 mg/kg), BaP alone (1, or 5 mg/kg), or DBP and BaP (50 + 1, or 250 + 5 mg/kg) for ninety days. More serious liver damage, including abnormal liver function, infiltration of inflammatory cells and disturbed secretion of inflammatory factors, were observed in long-term co-exposure to DBP and BaP group relative to those in single exposure group. Our data showed that long-term co-exposure to DBP and BaP induces macrophages to polarize toward M1 and inhibits polarization of M2 macrophages. Long-term co-exposure to DBP and BaP downregulated miR-34a-5p level and upregulated Notch signaling. These results indicated that imbalance in macrophages M1/M2 polarization mediated by activation of Notch signaling due to reduced miR-34a-5p level may contribute to additive effects on disorder of inflammatory factors secretion and subsequent liver injury following long-term DBP and BaP co-exposure.
人类常常长期暴露于复杂的环境污染物混合物中。据报道,邻苯二甲酸二丁酯(DBP)和苯并[a]芘(BaP)是两种典型的环境污染物,与肝损伤有关。然而,人们对 DBP 和 BaP 联合暴露对肝脏的影响知之甚少。在本研究中,大鼠连续 90 天暴露于 DBP(50 或 250mg/kg)、BaP(1 或 5mg/kg)或 DBP 和 BaP(50+1 或 250+5mg/kg)中。与单一暴露组相比,长期联合暴露于 DBP 和 BaP 的大鼠肝脏损伤更严重,包括肝功能异常、炎症细胞浸润和炎症因子分泌紊乱。我们的数据表明,DBP 和 BaP 的长期联合暴露诱导巨噬细胞向 M1 极化,并抑制 M2 巨噬细胞的极化。DBP 和 BaP 的长期联合暴露下调了 miR-34a-5p 水平并上调了 Notch 信号通路。这些结果表明,由于 miR-34a-5p 水平降低导致 Notch 信号通路激活,从而导致巨噬细胞 M1/M2 极化失衡,可能是 DBP 和 BaP 长期联合暴露导致炎症因子分泌紊乱和随后肝损伤的附加效应的原因。