由于其优良的物理和化学性能，镍（Ni）广泛应用于工业制造和日常生活中。然而，镍有可能损害动物的免疫系统，脾脏是典型的免疫器官。因此，了解NiCl2对脾脏损害的机制至关重要。本研究的目的是调查不同浓度的NiCl2暴露和强抗氧化剂干预对脾脏淋巴细胞的影响，以更好地了解Ni对脾脏淋巴细胞的损伤机制。在这个实验中，我们以小鼠脾脏淋巴细胞作为研究对象。我们首先测量了不同NiCl2浓度引起的氧化应激、炎症和坏死程序的程度。随后，我们添加强效抗氧化剂N-乙酰-L-半胱氨酸（NAC），并在随后的实验中使用过氧化氢（H2O2）作为阳性对照。我们的研究结果表明，NiCl2能够导致脾脏淋巴细胞产生大量的反应性氧化物质（ROS），这会降低抗氧化酶相关基因的mRNA水平，GSH-PX、SOD、T-AOC和MDA的变化，以及线粒体膜电位的变化。ROS会引发体内产生炎症反应，在免疫荧光实验中表现为肿瘤坏死因子（TNF-α），相关炎症基因的mRNA水平显著增加。在caspase 8抑制的情况下，TNF-α可通过RIP1、RIP3和MLKL介导的坏死程序的发生。AO/EB揭示，暴露于NiCl2的脾脏淋巴细胞有明显的坏死，RIP1、RIP3和MLKL的mRNA和蛋白水平显著增加。此外，研究结果表明，NAC作为抗氧化剂能够减轻暴露于NiCl2时引起的氧化应激、炎症和坏死程序。本研究的结果表明，NiCl2能够导致小鼠脾脏淋巴细胞发生氧化应激、炎症和坏死程序，其中部分可以通过NAC减轻。该研究为理解NiCl2的毒理效应提供了参考。研究表明，NAC可能在减少NiCl2对免疫系统的毒性方面有用。这项研究可能有助于制定有效的措施来预防和减轻NiCl2对免疫系统的毒性效应。版权所有 © 2023 张，徐，马，施，刘，宋，方，刘，乔，蔡和张。

Nickel (Ni) is widely used in industrial manufacturing and daily life due to its excellent physical and chemical properties. However, Ni has the potential to harm animals' immune system, and spleen is a typical immune organ. Therefore, it is crucial to understand the mechanism of NiCl2 damage to the spleen. The purpose of this study is to investigate the effects of different concentrations of NiCl2 exposure and intervening with strong antioxidants on spleen lymphocytes to better understand the damage mechanism of Ni on spleen lymphocytes.In this experiment, mice spleen lymphocytes were used as the research object. We first measured the degree of oxidative stress, inflammation, and necroptosis caused by different NiCl2 concentrations. Subsequently, we added the powerful antioxidant N-acetyl-L-cysteine (NAC) and used hydrogen peroxide (H2O2) as the positive control in subsequent experiments.Our findings demonstrated that NiCl2 could cause spleen lymphocytes to produce a large number of reactive oxygen species (ROS), which reduced the mRNA level of antioxidant enzyme-related genes, the changes in GSH-PX, SOD, T-AOC, and MDA, the same to the mitochondrial membrane potential. ROS caused the body to produce an inflammatory response, which was manifested by tumor necrosis factor (TNF-α) in an immunofluorescence experiment, and the mRNA level of related inflammatory genes significantly increased. In the case of caspase 8 inhibition, TNF-α could cause the occurrence of necroptosis mediated by RIP1, RIP3, and MLKL. AO/EB revealed that spleen lymphocytes exposed to NiCl2 had significant necroptosis, and the mRNA and protein levels of RIP1, RIP3, and MLKL increased significantly. Moreover, the findings demonstrated that NAC acted as an antioxidant to reduce oxidative stress, inflammation, and necroptosis caused by NiCl2 exposure.Our findings showed that NiCl2 could cause oxidative stress, inflammation, and necroptosis in mice spleen lymphocytes, which could be mitigated in part by NAC. The study provides a point of reference for understanding the toxicological effect of NiCl2. The study suggests that NAC may be useful in reducing the toxicological effect of NiCl2 on the immune system. The research may contribute to the development of effective measures to prevent and mitigate the toxicological effects of NiCl2 on the immune system.Copyright © 2023 Zhang, Xu, Ma, Shi, Liu, Song, Fang, Liu, Qiao, Cai and Zhang.