Iron accumulation is an important cause of various brain diseases. As a ferroxidase, ceruloplasmin (Cp) plays a key role in iron homeostasis and its abnormal activity leads to iron accumulation. However, the detailed biological function of Cp in brain iron homeostasis needs to be investigated. In this study, Cp knockout mice were prepared and the changes in iron content and protein expression related to iron metabolism were detected. The results showed that iron accumulation occurred in multiple tissues and organs of Cp knockout mice, but there was no obvious change in brain tissues. However, Cp deficiency affected the expression of many iron metabolism-related proteins in midbrain, such as DMT1+IRE, heavy chain ferritin (H-ferritin) and light chain ferritin (L-ferritin). Cp deficiency also impaired the behavioral ability of mice, including weakened exercise ability and reduced motor coordination. In vitro cell experiment indicated that the sensitivity of Cp knockout neuron and astrocyte to hypoxia was higher than that of wild type, which means Cp deficiency leads to the damage of cell self-protection. All these results confirm that Cp exerts a protective effect on the brain by regulating iron metabolism.

铁的积累是各种脑部疾病的重要原因。作为亚铁氧化物酶，铜蓝蛋白（Cp）在铁稳态中起关键作用，其异常活性导致铁积累。然而，需要研究 Cp 在脑铁稳态中的详细生物学功能。本研究制备Cp基因敲除小鼠，检测铁含量及与铁代谢相关的蛋白表达变化。结果表明，铁在Cp的多个组织和器官中发生积累。敲除小鼠，但脑组织无明显变化。然而，Cp缺乏影响中脑许多铁代谢相关蛋白的表达，如DMT1+IRE、重链铁蛋白（H-ferritin）和轻链铁蛋白（L-ferritin）。Cp 缺乏也会损害小鼠的行为能力，包括运动能力减弱和运动协调性降低。体外细胞实验表明，Cp敲除神经元和星形胶质细胞对缺氧的敏感性高于野生型，说明Cp缺乏导致细胞自我保护功能受损。所有这些结果证实Cp通过调节铁代谢对大脑发挥保护作用。