Objective: To observe the effects of chronic intermittent hypoxia (CIH) on myocardial cell apoptosis and explore the mechanism of microRNA-214 (miRNA-214) expression for myocardial cell apoptosis and cardiac dysfunction.
Methods: A total of 20 adult male Sprague-Dawley rats were randomized into two groups (n = 10 each): for CIH group, the rats were raised in a CIH chamber 8 h daily for 6 weeks; for normal control (NC) group, the animal were exposed to normoxic air 7 h daily for 6 weeks. Hemodynamic values and myocardial function were measured via a cannula inserted into right common carotid artery. Myocardial cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. The expressions of miRNA-214 and hypoxia-inducible factor-1α (HIF-1α) mRNA were observed by real-time polymerase chain reaction (PCR). The expressions of such apoptosis-related proteins as fatty acid synthase (Fas), caspase 3, caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2-Associated X Protein (Bax) were detected by Western blot.
Results: Compared with NC group, left ventricle end diastolic pressure (LVEDP) ((4.1 ± 0.5) vs (2.7 ± 0.4) mmHg, 1 mmHg = 0.133 kPa) increased, maximal rate of pressure decline (-dp/dtmax) ((3 005 ± 86) vs (5 918 ± 112) mmHg/s), maximal rate of pressure development (+dp/dtmax) ((4 118 ± 76) vs (7 547 ± 271) mmHg/s) and left ventricular systolic pressure (LVSP) ((90.7 ± 2.5) vs (132.7 ± 5.5) mmHg] decreased in CIH group (all P < 0.001). There were significantly more TUNEL positive cells in CIH group versus NC group (P < 0.001). The expression of miRNA-214 was significantly lower in CIH group than that in NC group (P < 0.001). In addition, HIF-1α mRNA level was significantly higher in CIH group than that in NC group (P < 0.001). The expressions of caspase 3, caspase 8, Fas and Bax increased significantly in CIH group versus NC group (all P < 0.001), suggesting increased apoptosis of myocardial cells in CIH group. Compared with NC group, the expression of Bcl-2 decreased significantly in CIH group (P < 0.001).
Conclusions: CIH may decrease the hemodynamic values and myocardial function in rats. The expression of miRNA-214 in CIH group is significantly depressed through accelerated apoptosis of myocardial cells.