This study aimed to investigate whether Cr(VI) induced tight joint and oxidative damage in the small intestine, as mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2)/reactive oxygen species (ROS)/Notch1 axis crosstalk. Thirty-two ICR mice were obtained and subjected to Cr(VI) via intragastric administration daily for 5 days. Western blot (WB) analysis, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) staining, and immunofluorescence (IF) staining were applied to detect small intestinal damage, Nrf2, Notch1, and respective downstream targets in this research. Results showed that Cr(VI) led to the tight joint and oxidative damage in the small intestine of mice. Nrf2 was stimulated, and Notch1 (Notch intracellular domain, NICD1) was activated to translocate into the nucleus and activate an antioxidant action. These findings were validated by WB analysis and IF staining. ROS levels increased as the Cr(VI) concentration increased. The colocalization analysis of Nrf2 and NICD1 implied that a crosstalk between Nrf2 and Notch1 existed. Therefore, this study indicated that the Nrf2/ROS/Notch1 axis crosstalk could aggravate the tight joint and oxidative damage in the small intestine after Cr(VI) treatment.

本研究旨在探讨 Cr(VI) 是否会通过核因子红细胞 2 相关因子 2 (Nrf2)/活性氧 (ROS)/Notch1 轴串扰介导，诱导小肠紧密连接和氧化损伤。获得 32 只 ICR 小鼠，每天通过灌胃给予 Cr(VI)，持续 5 天。本研究采用蛋白质印迹（WB）分析、酶联免疫吸附测定（ELISA）、免疫组织化学（IHC）染色和免疫荧光（IF）染色来检测小肠损伤、Nrf2、Notch1以及各自的下游靶标。结果表明，Cr(VI)导致小鼠小肠关节紧缩和氧化损伤。 Nrf2受到刺激，Notch1（Notch细胞内结构域，NICD1）被激活，易位到细胞核中并激活抗氧化作用。这些发现通过 WB 分析和 IF 染色得到验证。 ROS 水平随着 Cr(VI) 浓度的增加而增加。 Nrf2 和 NICD1 的共定位分析表明 Nrf2 和 Notch1 之间存在串扰。因此，本研究表明Nrf2/ROS/Notch1轴串扰会加重Cr(VI)治疗后小肠的紧密连接和氧化损伤。