Halofuginone improves myocardial ischemia/reperfusion arrhythmia by activating Nrf2/HO-1 signaling pathway in rats
Objective To explore the effect of halofuginone(HF)on myocardial ischemia-reperfusion arrhythmias in rats.Methods Thirty Wistar rats were randomly divided into Sham group,Model group and HF group,with 10 rats in each group.The left anterior descending coronary artery was ligation to establish the rat myocardial ischemia/reperfusion model.The rats in sham group were only ligation without ligation.At the same time,the rats in HF group were given sublingual intravenous injection(5 mg/kg),and the rats in Sham and Model groups were given equal volume of normal saline.The heart rate was measured every 5 minutes during ischemia and reperfusion.The area of myocardial injury was detected by TTC.The apoptosis of cardiomyocyte was detected by TUNEL staining.Activity of SOD and content of MDA in serum were detected by ELISA.The levels of Ca2+in rat myocardial tissue was detected.The expressions of Nrf2 and HO-1 in myocardial tissue of rats were detected by Western blot.Results HF decreased the heart rate during ischemia and increased the heart rate during reperfusion.HF decreased the myocardial infarction size,decreased the apoptosis rate of cardiomyocytes,increased activity of SOD in serum,down-regulated level of MDA in serum,down-regulated content of Ca2+in myocardial tissue,and activated Nrf2/HO-1 signaling pathway in MIRI rats.Conclusion HF could alleviate myocardial ischemia/reperfusion induced-myocardial oxidative damage and improve myocardial ischemia/reperfusion arrhythmia by activating Nrf2/HO-1 signaling pathway.