Abstract: The objective of this study was to investigate the role of endoplasmic reticulum stress (ERS) on citrinin-induced intestinal barrier dysfunction. Twenty-four 7-week-old Kunming mice weighed (27.8±1.5) g were divided into 4 groups randomly: control group(5% ethanol), citrinin of low-(1.25 mg·kg^－1), medium-(5 mg·kg^－1) and high-(20 mg·kg^－1) dose groups. After conventionally raised for one week, the mice in control group were administrated orally by 5% ethanol according to 0.1 mL·10 g^－1 body weight and the mice in toxin groups were exposed to different dosage of citrinin for 14 days. At the end of the experiment, the blood was collected, the serum was separated, the length of small intestine was measured and the jejunum samples were collected. The pathological changes of intestine were observed by HE staining, while the content of diamine oxidase (DAO), D-lactic acid(D-LA) and endotoxin (ET) were detected by ELISA. Besides, the activities of antioxidative enzymes and the release of reactive oxygen species (ROS) of jejunum were examined. In order to explore the role of ERS on citrinin-induced intestinal injury, 32 Kunming mice were randomly divided into 4 groups: control group(5% ethanol), medium-dose citrinin group (5 mg·kg^－1), 4-PBA group (240 mg·kg^－1) and citrinin + 4-PBA group. The mice were exposed to citrinin after intraperitoneal injection of 4-PBA for 1 h. The pathologic injury, oxidative damage, apoptosis and the expression of ER stress related proteins in jejunum were tested after 14 days. Besides, Spearman correlation analysis was used to determine the correlation between ERS signaling pathway and intestinal oxidative stress as well as intestinal barrier dysfunction. The results showed that different dosage of citrinin could trigger intestinal damage, oxidative stress and intestinal barrier dysfunction. Pretreated with 4-PBA up-regulated total antioxidant capacity (T-AOC) and the activities of catalase (CAT), total superoxide dismutase (T-SOD), decreased the production of ROS and malondialdehyde (MDA), inhibited cell apoptosis and ERS, down-regulated the content of DAO, D-LA and ET, increased the mRNA expression of ZO-1, Occludin and Claudin-1, finally relieved the damage of jejunum caused by citrinin. In addition, the endoplasmic reticulum stress signaling pathway was significantly correlated with intestinal oxidative stress and intestinal barrier dysfunction. In summary, the study indicated that ERS plays an important regulatory role in citrinin-caused barrier dysfunction of jejunum.

Key words: citrinin, endoplasmic reticulum stress, oxidative stress, apoptosis, intestinal barrier dysfunction