Effect of dynamin-related protein 1 in rats with myocardial ischemia/reperfusion injury

Abstract

To investigate the protective effect of dynamin-related protein 1 (Drp1) in rats with myocardial ischemia/reperfusion injury (IRI). Twenty-four healthy male Wistar rats were randomly divided into three groups (n = 8 each): sham group, IRI model group, and Drp1 inhibitor group. The left anterior descending branch of coronary artery was ligated to produce myocardial ischemia for 30 minutes and reperfusion injury model. Sham group was received only threading without ligation. The Drp1 inhibitor group was injected with 1.2 mg/kg mitochondrial division inhibitor 1 (mdivi-1) at 15 minutes before operation. At 3 hours after reperfusion, hemodynamics, serum myocardial enzymes, mitochondrial membrane potential (MMP), hydrogen peroxide (H2O2), reactive oxygen species (ROS) and ATP production were measured in rats. The myocardial tissues were harvested for the determination of the area at risk (AAR) and the infarct area (AI), and the ratio of AI/AAR was calculated. The expression of Drp1 and cytochrome C (Cyt C) was determined by Western Blot. Compared with the sham group, the left ventricular end diastolic pressure (LVEDP), cardiac troponin I (cTnI), MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), AI/AAR, H2O2, ROS, protein expression of Drp1 and Cyt C were significantly increased, left ventricular end systolic pressure (LVESP), ejection fraction (EF), fractional shortening (FS), MMP, ATP generation, expression of mitochondrial Cyt C were significantly decreased in IRI model group. Compared with IRI model group, LVEDP was significantly decreased in Drp1 inhibitor group [mmHg (1 mmHg = 0.133 kPa): 8.83±1.20 vs. 16.48±1.80], LVESP, EF, FS were significantly increased [LVESP (mmHg): 116.80±9.78 vs. 87.80±8.82, EF: 0.78±0.11 vs. 0.58±0.07, FS: (48.6±4.1)% vs. (32.4±3.2)%]; myocardial enzymes, H2O2 and ROS were significantly decreased in Drp1 inhibitor group [cTnI (ng/L): 31.9±8.8 vs. 49.2±13.7, CK-MB (U/L): 4.83±1.30 vs. 7.48±2.20, LDH (U/L): 1 327.80±280.20 vs. 1 858.80±324.80, H2O2: 6.40±1.40 vs. 8.90±1.50, ROS: 41 916.3±6 295.3 vs. 65 182.6±3 777.8], AI/AAR was significantly decreased (0.38±0.01 vs. 0.62±0.01), MMP and ATP were significantly increased [MMP: 0.78±0.13 vs. 0.38±0.07, ATP (μmol/g): 150.8±12.3 vs. 103.7±8.4], the expression of Drp1 was significantly decreased (0.50±0.02 vs. 0.79±0.05), expression of mitochondria Cyt C was significantly increased (0.64±0.04 vs. 0.21±0.01), and expression of cytoplasmic Cyt C was significantly decreased (0.48±0.03 vs. 0.78±0.04), and the differences were statistically significant (all P < 0.05). Mitochondrial fission was excessively high during IRI, and its function was significantly decreased. Drp1 inhibitor could inhibit the division of mitochondria, and improve its function and cardiac function.