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.
RESULTS: 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).
CONCLUSIONS: 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.