A novel 14-amino acid peptide from yak alleviates kidney damage in the rat model of myocardial ischemia-reperfusion

Myocardial ischemia-reperfusion (MI/R) not only causes cardiac damage, but also causes severe renal damage. T8 is the 8th peptide identified by peptiomics in digested yak milk dregs and our previous studies showed that T8 had strong antioxidant activity. This study evaluated the protective effects and molecular mechanisms of MI/Rinduced kidney injury in rats. Our results indicated that peptide T8 could increase ejection fraction (EF) and shortened fraction (FS), and degraded ST segment elevation, which ameliorated cardiac function in the MI/R rats. Peptide T8 could increase activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and decreased the contents of malondialdehyde (MDA), serum creatinine (Scr) and blood urea nitrogen (BUN), which could ameliorate renal insufficiency. Peptide T8 and kidney injury-related targets in the MI/R-damaged rats were obtained from network pharmacology analysis. KEGG analysis revealed that T8 might affect 54 signaling pathways and 13 key targets were obtained by PPI network analysis. The binding affinity of peptide T8 to Keap1 was found to be the strongest by molecular docking analysis. In the H2O2-induced HEK293 cell model, peptide T8 decreased reactive oxygen species (ROS) content and changed the expression ratio of Bcl-2 and Bax, thereby inhibiting mitochondria-dependent apoptosis. Further studies indicated that T8 could regulate Nrf2 pathway and downstream target genes such as NQO1, which could reduce oxidative stress-induced damage. These results suggest that peptide T 8 can exert renal protection via regulating Nrf2 pathway and apoptosisrelated genes.