Mechanism Of Allo In Improving Cardiac Function In Chronic Heart Failure

Objective To explore the mechanism of allopurinol (ALLO) in improving cardiac function via myocardial energy metabolism in rats with heart failure.Methods 35 male SD rats were randomly arranged into the ALLO Group (experimental animal models, treated with 50 mg/kg·d ALLO by gavage, n=12), the AMI Group (experimental animal models, treated with saline by gavage, n=13) and the Sham-Operated Group (sham-operated, treated with NS by gavage, n=10). SD rats in ALLO Group and the AMI Group were established of acute myocardial infarction (AMI) models by ligation of the left anterior descending coronary artery, and SD rats of sham-operated group underwent the same procedure except ligation of LAD. Two days after surgery, all of the animals were treated with administration by gavage as the above protocol. Eight weeks later, the cardiac functions of the animals were estimated by echocardiography (UCG) in vivo, the content of Malondialdehyde (MDA) in serum of myocardial tissue was measured by barbituric acid method. The brain natriuretic peptide(BNP)content of venous blood was detected by ELISA. The activities of mitochondrial respiratory chain enzyme complex I to IV were detected by biochemical methods, The expression of XO、PGC-1α CPT-1 and GLUT4 mRNA in non-infarct area of left ventricular was detected by real-time fluorescent quantitative PCR. Expression of protein of XO、PGC-1α、CPT-1 and GLUT4 was detected by western blotting. The myocardial morphological changes were observed by HE staining, and ultrastructure changes of myocardial cells were detected by transmission electron microscope.Results Compared with the rats in sham-operated group, rats in model groups showed poor cardiac function(P<0.05), significant decrease of the activity of mitochondrial complex Ⅰ、Ⅲ、Ⅳ(P<0.05), increased BNP content and MDA level(P<0.05), mRNA of XO、GLUT4 in cardiac tissue of rats increased in the ALLO Group and in the AMI Group (P<0.05), and mRNA content of PGC-la decreased in the ALLO Group and in the AMI Group (P<0.05), and mRNA content of CPT-1 decreased in the AMI Group (P<0.05). Protein expression of XO in cardiac tissue of rats increased (P<0.05), and the protein expression level of PGC-1α decreased in the ALLO Group and in the AMI Group (P<0.05), and the protein expression of GLUT4 increased, and the protein expression of CPT-1 decreased in the AMI Group (P<0.05). There is no difference between sham-operated group and ALLO Group. Tissue morphology analysis showed loose and edematous tissue by HE staining and it was also observed lysis of myocardial filament, swollen and bubbled mitochondria under electron microscopy in the model groups than that in the sham-operated group. While compared with AMI group, rats in ALLO treatment group showed better cardiac function(P><0.05), increased activity of mitochondrial complex Ⅰ、Ⅲ、 IV(P<0.05), decreased BNP content and MDA level(P<0.05), mRNA of XO、GLUT4 decreased (P<0.05), and mRNA content of PGC-1α、CPT-1 increased (P<0.05). the protein expression of XO、GLUT4 decreased (P<0.05), and the protein expression of PGC-1 a. CPT-1 increased (P<0.05) in the ALLO Group, loose and swollen tissue was alleviated, lysis of myocardial filament and swollen mitochondria was also alleviated.Conclusion ALLO could improve cardiac function in rats with chronic heart failure, which may be involved in increasing the activities of mitochondrial respiratory chain enzyme and regulating PGC-la in glucolipid metabolism.