IMPROVEMENT OF MYOCARDIAL ENERGY METABOLISM IN HYPOBARIC HYPOXIA EXPOSED RATS BY POLYGONATUM SIBIRICUM POLYSACCHARIDES
Objective To investigate the regulatory effect of Polygonatum sibiricum polysaccharides(PSP)on myocardial energy metabolism in hypobaric hypoxia exposed rats and explore its mechanism.Methods Twenty-four Wistar rats were randomly divided into control group(control),hypobaric hypoxia group(HH)and hypobaric hypoxia+PSP group(HH+PSP)with eight rats in each group.Rats in the HH and HH+PSP groups were subjected to chronic HH exposure for 2 weeks in a hypobaric chamber at a simulated altitude of 6000m.The HH+PSP group was given 400mg/kg PSP and the other two groups were given equal volume of saline.The body weight and food intake were measured twice a week,and cardiac function was measured by echocardiography at the end of the experiment.Determination of free fatty acids(FFA),glucose(GLU),acetyl coenzyme A(A-CoA)and adenosine triphosphate(ATP)in serum and myocardial tissues was carried out to evaluate energy metabolism.The expression levels of peroxisome proliferator activated receptor alpha(PPARα),carnitine palmitoyltransferase 1(CPT-1),pyruvate dehydrogenase kinase 4(PDK4),glucose transporter(GLUT4)and glyceraldehyde-3-phosphate dehydrogenase(GAPDH)in rat myocardial tissue were examined by Western blotting.Results Compared with control group,rats in the HH group had significantly lower body weight and food intake(P<0.05).Echocardiography showed lower cardiac output,ventricular end volume and stroke volume(P<0.05),while ventricular posterior wall thickness was significantly higher.Energy metabolism-related indexes showed significantly lower GLU and ATP(P<0.05),and significantly higher FFA and A-CoA contents(P<0.05).Western blotting of myocardial tissue proteins showed significantly decreased expression levels of PPARα,CPT-1,PDK4(P<0.05)and significantly increased expression levels of GLUT4 and GAPDH(P<0.05).Compared with the HH group,there were no significant changes in body weight and food intake in the HH+PSP group(P>0.05).Cardiac output,ventricular end volume and stroke volume were improved(P<0.05),and ventricular posterior wall thickness was decreased(P<0.05).GLU and ATP levels were significantly increased(P<0.05),and FFA and A-CoA levels were significantly decreased(P<0.05).PPARα,CPT-1,PDK4,GLUT4 and GAPDH protein expression levels were significantly down-regulated(P<0.05).Conclusion Cardiac malfunction caused by HH exposure is closely related to the disturbance of energy metabolism in rats.The intervention of PSP can significantly improve myocardial energy metabolism and cardiac function after HH exposure,which may be related to the changes of the expression of PPARα-CPT-1/PDK4,GLUT4 and GAPDH in myocardial tissues.