Qian Honghao, Zhao Yaming, Wang Yiming, Zhao Haotang, Cui Jianwei, Wang Ziyu, Ye Hui, Fang Xiaoqi, Ge Zhili, Zhang Yuezhu, Ye Lin
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China.
Department of Anatomy, School of Basic Medicine, Jilin University, Changchun, China.
Toxicology. 2024 Jan;501:153696. doi: 10.1016/j.tox.2023.153696. Epub 2023 Dec 6.
Atrazine (ATR) is a widely used herbicide and due to its persistence in environment and bioaccumulation, it can cause harmful impacts on human health. ATR exposure can lead to disorders of lipid metabolism in the liver, but its underlying mechanism is still unclear. 40 eight-week-old rats were given different doses of ATR (0, 0.5, 5 and 50 mg/kg/d) for 90 days. The liver tissue and serum were collected for histological observation and biochemical analysis. The levels of lipid and oxidative stress were assessed using colorimetry. Changes in MMP and ROS of liver cells were observed through flow cytometry. The expression of mRNA and protein was detected using Real-Time PCR and western blot. The results showed that TC and HDL-C levels in both the liver and serum were increased in the ATR-treated groups. The levels of MDA were accumulated, while the levels of SOD and GSH were depleted in the liver with ATR exposure. The expression of liver lipid metabolism related genes (SCD1, DGAT2, ACC1, PPARγ) was elevated. The liver ERS was activated and the gene expression of IRE1α/XBP1 signal pathway and GRP78, GRP94 in the liver was increased. There was a correlation between the levels of ERS and the levels of lipid metabolism. These results suggested that ATR can activate ERS and promote the expression of IRE1α/XBP1 signaling pathway, and further lead to lipid metabolism disorders in rat liver. This study can provide valuable insights as a reference for the prevention and control of hazards associated with agricultural residues.
莠去津（ATR）是一种广泛使用的除草剂，由于其在环境中的持久性和生物累积性，会对人类健康造成有害影响。接触ATR会导致肝脏脂质代谢紊乱，但其潜在机制仍不清楚。将40只8周龄大鼠给予不同剂量的ATR（0、0.5、5和50毫克/千克/天），持续90天。收集肝脏组织和血清进行组织学观察和生化分析。使用比色法评估脂质和氧化应激水平。通过流式细胞术观察肝细胞的线粒体膜电位（MMP）和活性氧（ROS）变化。使用实时荧光定量聚合酶链反应（Real-Time PCR）和蛋白质免疫印迹法（western blot）检测mRNA和蛋白质的表达。结果表明，ATR处理组肝脏和血清中的总胆固醇（TC）和高密度脂蛋白胆固醇（HDL-C）水平均升高。随着ATR暴露，肝脏中丙二醛（MDA）水平积累，而超氧化物歧化酶（SOD）和谷胱甘肽（GSH）水平降低。肝脏脂质代谢相关基因（硬脂酰辅酶A去饱和酶1（SCD1）、二酰甘油酰基转移酶2（DGAT2）、乙酰辅酶A羧化酶1（ACC1）、过氧化物酶体增殖物激活受体γ（PPARγ））的表达升高。肝脏内质网应激（ERS）被激活，肝脏中肌醇需求酶1α（IRE1α）/X盒结合蛋白1（XBP1）信号通路以及葡萄糖调节蛋白78（GRP78）、葡萄糖调节蛋白94（GRP94）的基因表达增加。ERS水平与脂质代谢水平之间存在相关性。这些结果表明，ATR可激活ERS并促进IRE1α/XBP1信号通路的表达，进而导致大鼠肝脏脂质代谢紊乱。本研究可为防控农业残留相关危害提供有价值的参考见解。
