不同来源硒对镉致肠损伤的保护作用及机制研究

Objective To investigate the protective effects of chemical-based selenium (selenocystine, SeCys2) and plant-based selenium (Cardamine hupingshanensis-Se, HUP) on cadmium (Cd)-induced intestinal injury and the underlying mechanism. Methods Cd-enriched (HUP-Cd) and Se-Cd-coenriched (HUP-Cd+Se) plants were obtained by hydroponics. C57BL/6 mice were randomly divided into the control (Con), Cd, Cd+Se, HUP-Cd, and HUP-Cd+Se groups. The mice in the Cd group were gavaged by CdCl2 solution [Cd: 1.2 mg/kg body weight (BW), and mice in the Cd+Se group were gavaged by CdCl2 and SeCys2 solution (Cd: 1.2 mg/kg BW; Se: 0.4mg/kg BW). The mice in the HUP-Cd and HUP-Cd+Se groups were gavaged by corresponding suspensions containing the same amount of Cd and/or Se used in the Cd and Se groups. After 12 weeks, feces, serum and duodenum were collected. Histopathological observation was performed to examine the pathological changes and the number of goblet cells in the duodenum. Immunohistochemistry was used to analyze Ki67 and Lgr5 positive cells in the crypts. Western blot was conducted to determine the phosphorylation levels of cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) and their downstream proteins, as well as the expression levels of tight junction proteins Occludin, Claudin1 and ZO-1. qPCR was employed to detect the mRNA expression levels of inflammatory factors (IFN-β、IFN-γ、TNF-α、IL-6). Results Compared with the Cd and HUP-Cd groups, the mice in the Cd+Se and HUP-Cd+Se groups had lower serum levels of Cd with higher amount of Cd in the feces. Cd exposure induced obvious intestinal injury. Se and HUP-Se intervention alleviated oxidative stress, improved intestinal pathological injury, and upregulated the expression of tight junction proteins in the duodenum. Cd exposure activated the cGAS/STING pathway. Se and HUP-Se intervention downregulated the phosphorylation of proteins in this pathway and the mRNA expression levels of downstream inflammatory factors. Conclusion Chemical- and plant-based Se alleviated Cd-induced intestinal injury in mice by downregulating cGAS/STING pathway and inflammatory factors.