重金属污染严重影响水域环境和生物。铜（Cu）和镉（Cd）是最常见的重金属污染物之一，会对水生生物的生存、发育和繁殖造成损害。随着农业和工业的发展，存在着东北白鱼（Coregonus ussuriensis Berg）水源中的重金属污染可能性。然而，对于东北白鱼的毒性尚未有发表的研究。对东北白鱼进行的急性毒性实验显示，铜和镉的96小时半数致死浓度分别为0.492 mg/L（95%可信区间：0.452-0.529）和1.548 mg/L（95%可信区间：1.434-1.657），安全浓度分别为4.92 µg/L 和15.48 µg/L。随后，将东北白鱼分别处理96小时，使用Cu（96小时LC50的20%）、Cd（96小时LC50的20%）和Cu 95% LC50及Cd 95% LC50的20%混合处理。使用苏木精和伊红染色验证了这三种不同暴露方式对东北白鱼肝脏和鳃的组织所造成的组织学损伤。与参照组相比，这三种暴露方式均导致了东北白鱼肝脏组织的不同程度空泡变性、核浓缩和坏死，以及鳃组织的水肿、过度增生、板层融合和上皮上升。损伤的严重程度随暴露时间的增加而增加。使用酶活性检测试剂盒测定了鳃和肝组织的抗氧化酶活性，以反映受到铜和镉暴露（单独或组合）引发的氧化应激。超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH）的酶活性与参照组相比明显增高。然而，这些酶的活性随着暴露时间的增加而下降。与参照组相比，丙二醛（MDA）活性在暴露期间显著增加。采用实时逆转录聚合酶链反应（RT-PCR）分析东北白鱼鳃和肝组织的免疫基因表达。促炎性细胞因子白介素一β（IL-1β）和肿瘤坏死因子-α（TNF-α）的表达水平与暴露时间呈正相关，并随着暴露时间的增加而显著上调。金属硫蛋白（MT）基因表达水平在暴露后的短期内显著上调，但随着暴露时间的增加而下调。我们的结果表明，暴露于水中的铜和镉溶液，无论单独或组合，均会引起东北白鱼鳃和肝组织的组织病理损伤、氧化应激和免疫毒性。本研究调查了铜和镉对东北白鱼的毒性作用，以促进健康水产养殖中对水源中的重金属进行监测。© 2023. 作者，独家许可给Springer Science+Business Media, LLC，Springer Nature的一部分。

Heavy metal contamination severely affects the aquatic environment and organisms. Copper (Cu) and cadmium (Cd) are two of the most common heavy metal contaminants that impair the survival, development, and reproduction of aquatic organisms. With the growth of agriculture and industry, there is a possibility of heavy metal pollution in Coregonus ussuriensis Berg's water source. However, there are no published studies on the toxicity to C. ussuriensis. Acute toxicity experiments in C. ussuriensis revealed the 96-h median lethal concentrations of copper and cadmium to be 0.492 mg·L-1 (95% confidence interval: 0.452-0.529) and 1.548 mg·L-1 (95% confidence interval: 1.434-1.657), respectively, and safe concentrations of 4.92 µg·L-1 and 15.48 µg·L-1, respectively. C. ussuriensis was then treated for 96 h with Cu (20% of 96 h LC50), Cd (20% of 96 h LC50), and a combination of Cu and Cd (20% of Cu 96 h LC50 + 20% of Cd 96 h LC50). The histological damage caused by the three different exposure modes to the liver and gills of C. ussuriensis was verified using hematoxylin and eosin staining. All three exposure modes caused different degrees of vacuolization, nuclear consolidation, and necrosis in the liver tissue of C. ussuriensis and edema, hyperplasia, laminar fusion, and epithelial elevation in the gill tissue compared with the reference group. The severity of the damage increased with increasing exposure time. Anti-oxidant activity in the gill and liver tissues were measured using enzyme activity assay kits to reflect oxidative stress induced by copper and cadmium exposure alone and in combination. The enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH) were substantially higher than those in the reference groups. However, the activities of the enzymes decreased with increasing exposure time. Malondialdehyde (MDA) activity significantly increased during exposure in relation to that in the reference group. Analysis of immune gene expression in C. ussuriensis gill and liver tissues was executed using real-time inverse transcript polymerase chain response (RT-PCR). The expression levels of the pro-inflammatory cytokines interleukin one beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) were positively correlated with exposure time and were significantly upregulated with increasing exposure time. Metallothionein (MT) gene expression levels were significantly upregulated in the short term after exposure compared to the reference group but decreased with increasing exposure time. Our results indicate that exposure to aqueous copper and cadmium solutions, either alone or in combination, causes histopathological damage, oxidative stress, and immunotoxicity in C. ussuriensis gill and liver tissue. This study investigated the toxic effects of copper and cadmium on C. ussuriensis to facilitate the monitoring of heavy metals in water sources for healthy aquaculture.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.