Mechanism study of orientin protecting rat heart from myocardial ischemia/reperfusion injury based on mitochondrial quality control / 中草药

ABSTRACT

Objective To investigate the regulation effects of orientin on mitochondrial quality control in cardiomyocytes of rats with myocardial ischemia/reperfusion injury (MIRI). Methods A total of 75 Sprague-Dawley male rats were randomly divided into five groups sham group, model group, and orientin preconditioning groups (1.0, 2.0, and 4.0 mg/kg). Except for sham group, all rats were exposed to modeling of MIRI with ligation of left anterior descending coronary artery (LADCA) for 30 min, and then releasing for 120 min. Mitochondrial membrane potential (MMP) and opening of mitochondrial permeability transition pore (mPTP) were detected by Microplate Reader; Activity of mitochondrial respiratory chain complexes I-IV was detected by Spectrophotometer; Cardiomyocyte apoptosis was detected by TUNEL method; Apoptosis and mitophagy related proteins were detected by Western Blot and the interaction between Parkin and p62 on mitochondria were detected by Co-IP. Results Orientin significantly restored MMP, mPTP opening threshold and activity of mitochondrial respiratory chain complexes I-IV, and reduced cardiomyocyte apoptosis. Additionally, orientin can dramatically inhibit the protein expression level apoptosis and mitophagy related proteins and weaken the interaction between Parkin and p62. Conclusion Orientin has a significant protective effect on cardiomyocyte mitochondria in MIRI rats. Its underlying mechanism is related to inhibition of hyperactivity of mitophagy in cardiomyocytes via Parkin-dependent and Parkin-independent signaling pathways.