Abstract

The occurrence and development of diabetes seriously threaten the health of patients. Therefore, the mechanism exploration of diabetes is of great significance for more effective control of this disease. In this study, we aimed to investigate the regulatory mechanism of miR-139-5p and Notch signaling pathway on liver damage and oxidative stress in diabetic mice. The mouse model of diabetes was established, and the mice were divided into normal group, model group, negative control (NC) group, miR-139-5p mimic group, miR-139-5p inhibitor group, DAPT group, and miR-139-5p inhibitor + DAPT group. The mRNA expressions of miR-139-5p, Notch1, Jagged1, and NICD1, and the protein expressions of Notch1, Jagged1, and NICD1 were detected. In addition, HepG2 cells were cultured for high glucose induction, and cell cycle distribution and apoptosis were detected by flow cytometry. The results showed that the body weights of mice in the model, NC, miR-139-5p mimic, miR-139-5p inhibitor, DAPT, and miR-139-5p inhibitor + DAPT groups were all lower than that in the normal group. Co-localization of miR-139-5p and Notch1 was observed in the fluorescence in situ hybridization assay, and miR-139-5p was found to negatively regulate Notch1. Furthermore, reduced blood glucose level and inhibited liver oxidative stress were observed in mice with miR-139-5p overexpression or DAPT treatment. DAPT treatment reversed the increase of blood glucose level and oxidative stress injury caused by miR-139-5p silencing. In conclusion, up-regulation of miR-139-5p expression can protect liver tissue from oxidative stress injury in diabetic mice, and its mechanism may be related to the inhibition of Notch signaling pathway.