Molecular Basis Of Effects Of Aerobic Exercise On Cardiac Function In Rats With Early Heart Failure Due To Pressure Load

Objective: The related research of our laboratory found that aerobic exercise can delay the process of pressure load in the rat heartfailure effectively, improve the symptoms of heart failure. This improvement is based on aerobic exercise on the regulation of myocardial mitochondrial function, especially for the regulation of mitochondrial respiratory chain complex I’s activity. The purpose of this study is to investigate the regulation that the aerobic exercise affect the rat cardiac function of early heart failure caused by pressure load, and the relationship between the mitochondrial biosynthesis and the quality control. we will explore the molecular mechanism of aerobic exercise intervention from the point of view.Methods: We use the male rats of Wistar for materials, then made the pressure load model after the surgery of abdomidol aorta, and raised from 8 weeks to the occurrence of chronic heart failure. The control group(Sham) is without the characterization of heart failure. Chronic heart failure rats were randomly divided into the quiet group of surgery(Rest) and the exercise group of surgery(Exer), then continue to raise eight weeks with control group, the rats of Sham group and Rest group were free, but Exer group processd the training of aerobic exercise. the way of the training is treadmill running, and the exercise intensity is 20 m/min, 1 hour a day, 5 days a week. After the training of aerobic exercise, we take heart left ventricle of each rat, then use the method of Southern Blot for determination of mitochondrial DNA copy number in myocardial cells, and use the mothod of Western Blot for detection of mitochondrial protein involved in biosynthesis and quality control.Results:1. Compared with the Sham group, the Rest group’s mt DNA copy number increased significantly, and there is not difference between the Exer group mt DNA copy number and Sham group;2. In the heart failure group(Rest) of rats, following the increase of mt DNA copynumber, the expression of ND1 and ATP6 increased yet. And the both protein are encoded by mitochondrial genes. And the expression of COX and ATP5AⅣ decreased insteadly, but the expression of SDHB increased insteadly, all of these protein are encoded by nuclear genes. Transcription factor TFAM and regulating factor PGC1 alpha’ expression decreased significantly; Compared with Rest group, mitochondrial DNA copy number of Exer group rats reduced, at the same tim, the expression of ND1 reduced yet, the expression of ATP6 increased instead. Nuclear encoded COX Ⅳ, ATP5 A, SDHB and the expression of TFAM did not have significant changes. Compared with the Rest group, the expression levels of PGC1 alpha in the Exer group increased and tend to Sham group;3. compared with the Sham group, the Rest group rats fusion protein Mfn1, Mfn2, OPA1 and the expression of split protein Drp1, Fis1 decreased; Compared with Rest group, these fusion and fission proteins of Exer group did not have significant changes;4. Compared with the Sham group, the expression of LC-3, Fundc1, Atg5 decreased in chronic heart failure rats, the value of LC-3b/LC-3a also fell. Aerobic exercise training make the expression of LC-3 and Fundc1 of chronic heart failure rats increased, the value of LC-3b/LC-3a also increased, but the expression of Atg5 did not have difference.Conclusion:(1) Mitochondrial DNA and its coding protein increased in chronic heart failure rats, but the mitochondrial protein encoded by nuclear genes reduced(except SDHB), mitochondrial encoding protein and nuclear encoding protein do not have consistent, so the total number of mitochondria do not increased; Continuous aerobic exercise can not adjust the myocardial mitochondria of chronic heart failure rat caused by pressure load, only adjust to biosynthesis of the specific protein, so as to alleviate the process of heart failure;(2) The intervention of continues aerobic exercise in rats of early heart failure caused by pressure load did not have relationship with the myocardial mitochondriafusion and fission;(3) Continuous aerobic exercise by effectively improve LC-3 and Fundc1 protein expression and increase the proportion of LC-3b increased mitochondrial autophagy ability of chronic heart failure rats, so as to remove damaged mitochondria.(4) In the process of aerobic exercise on the intervention of chronic heart failure, by PGC1 alpha on mitochondrial biosynthesis and the regulation of autophagy plays a big role.