Abstract：
We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y-maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS-Na displayed some antagonistic effects against the Mn- and Fe-induced synaptic structural damage, growth, learning and memory impairment.
摘要：
我们建立了体外和体内锰（Mn）和铁（Fe）暴露的实验模型，并讨论了锰和铁联合暴露对嗜铬细胞瘤来源的细胞系12（PC12）细胞和大鼠皮质的突触功能的影响，分别。我们研究了对氨基水杨酸钠（PAS-Na）对锰和铁联合神经毒性的保护作用，为锰铁联合神经毒性的防治提供科学依据。采用Westernblot和逆转录-定量聚合酶链反应(RT-qPCR)检测突触损伤相关蛋白和mRNA的表达水平。采用Y-迷宫新颖性试验和平衡木试验评价大鼠运动和认知功能。采用苏木精、伊红(H&E)和Nissl染色观察大鼠皮质损伤情况。结果表明,大鼠体内锰、铁的联合暴露能产生协同作用,削弱生长和发育，改变学习和记忆以及运动功能。Mn和Fe的结合也对PC12细胞的突触结构造成损伤，表现为树突和轴突末端的肿胀，甚至导致细胞死亡.PAS-Na对锰和铁诱导的突触结构损伤表现出一些拮抗作用，增长,学习和记忆障碍。
