College of Veterinary Medicine, Shandong Agricultural University, Tai`an, Shandong, 271018, China.
Research Center for Animal Disease Control Engineering, Shandong Agricultural University, Tai`an, Shandong, 271018, China.
Environ Toxicol Pharmacol. 2021 Jul;85:103640. doi: 10.1016/j.etap.2021.103640. Epub 2021 Mar 20.
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.
本研究旨在探讨六价铬（Cr(VI)）是否通过核因子红细胞 2 相关因子 2（Nrf2）/活性氧（ROS）/Notch1 轴串扰介导，引起小肠紧密连接和氧化损伤。将 32 只 ICR 小鼠通过灌胃每日给予 Cr(VI)处理，共 5 天。本研究应用 Western blot（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 及其各自下游靶点。结果表明，Cr(VI)导致了小鼠小肠的紧密连接和氧化损伤。Nrf2 被激活，Notch1（Notch 细胞内结构域，NICD1）被激活并转位到细胞核，激活抗氧化作用。WB 分析和 IF 染色验证了这些发现。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 轴串扰可能会加重 Cr(VI)处理后小肠的紧密连接和氧化损伤。
