Luteolin Regulates Mitophagy to Alleviate Myocardial Ischemia-Reperfusion Injury via Sirt3/Foxo3a Pathway.

Abstract

Luteolin (LUT) belongs to a kind of flavonoid, which has protective effects on myocardial ischemia/reperfusion (I/R) injury. Sirt3 is located in mitochondria and interacts with Foxo3a to protect mitochondrial function against stress. Mitophagy is an important form of mitochondrial quality control. However, whether LUT regulates mitophagy to alleviate myocardial I/R injury via the Sirt3/Foxo3a pathway is rarely reported. In this study, 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) is used to inhibit the Sirt3/Foxo3a pathway. Male adult rats are divided into four groups: Sham group, I/R group, I/R+LUT group, and I/R+LUT+3-TYP group. The I/R rats model is established by ligating the left anterior descending coronary artery for 30 min, then releasing the ligature for 24 h. Indexes of left ventricular function, myocardial damage, oxidative stress, and mitophagy are detected. It is found that LUT treatment activated Sirt3/Foxo3a pathway, improves left ventricular function, decreases myocardial infarction size, inhibits myocardial apoptosis and oxidative stress, and initiates mitophagy in I/R rats. Moreover, these protective effects of LUT are weakened when Sirt3 is inhibited. Together, LUT regulates mitophagy to alleviate myocardial I/R injury via the Sirt3/Foxo3a pathway.