Effects Of Long-term Aerobic Exercise On The Changes Of Myocardial Autophagy In Young SHR Rats And Its Mechanism Of Action

Research objective:With the improvement of economic level and the change of life style, the incidence of hypertension is gradually increasing, which is seriously harmful to people's health. Hypertension is closely related to chronic cardiac dysfunction. Hypertension manifested by loss of heart muscle cells, ventricular dilatation, the decline to pump blood. Severe high blood pressure can lead to heart failure and even death. Autophagy is an important mechanism for the maintenance of homeostasis and the renewal of eukaryotic cells. Myocardial autophagy plays an important role in the maintenance of cardiac function.The study shows that in the myocardium of aging rats, the left ventricular wall had severe fibrosis, the ventricular wall was thickened, the number of myocardial cells decreased, and testing found that the myocardial levels of Autophagy has declined. After knocking down the autophagy initiation factor Atg5, cardiac hypertrophy, ventricular dilation and systolic dysfunction were induced in the heart of mice. Moderate exercise can improve cardiac structure and function in hypertension-induced damage. It is not clear whether exercise can improve cardiac function by altering the level of autophagy in myocardial cells and improving blood pressure.This article is designed to determine the alterations of autophagy in 16-weeks cardiac muscle with SHR,and to observe the effect of long-term aerobic exercise on the autophayg related proteins' and genes' expression,to provide theoretical basis and experimental support for the prevention and treatment of hypertension.Research methods:18 4-week old WKY rats were randomly divided into WKY control group(Group WKY, n=7) and WKY exercise group(Group WE, n=9).20 4-week old SHR rat were randomly divided into SHR control group(Group SHR, n=9)and SHR exercise group(Group SE, n=11). After adaptive feeding a week, the exercise group rats were trained for 9 weeks, six days per week. During the first week of swimming training, 15min on the first day, and the next day 30min,90min to increment it to the sixth day. Starting from the second week, rats in group WE and SE were both asked to swim for 90min with non-weight bearing everyday, which continues 8 weeks. After the end of the exercise, the changes of cardiac function were detected by left ventricular catheterization. The structure of rat cardiac muscle cells was observed by transmission electron microscope. Test the changes of protein expression levels of LC3, Beclinl and p62 by Western blot and the changes of mRNA by qRT-PCR.Research results:1) Histological results showed that compared with the WKY, myocardial fibers were significantly thicker and closely spaced in the WE; myocardial cells arranged loose disorder, myocardial fiber breakage, fused into a wave shape in the SHR. Compared with the SHR, the myocardial cells were more regular and the pathological injury was significantly reduced in the SE.2) Transmission electron microscopy showed that compared with the WKY, myocardial fibers arranged disorderly, sarcomere structure was destroyed, Z line fault and presents a wave shape, the number of mitochondria increased within muscle original fiber arranged disorder, muscle section structure damage, z line fracture, rendering out wave-like, part regional of muscle silk dissolved disappeared, and was hyperplasia of mitochondrial replaced, mitochondrial form exception, arrangement no law in the SHR; compared with the SHR, myocardial sarcomere light and dark bands were clear, olderly arranged in the majority of mitochondria in the SE, compact and morphology of myocardial tissue close to the WKY. These results suggested that the myocardial fiber structure was damaged in the SHR, and the aerobic exercise could reduce the damage of the myocardial fiber structure.3) Cardiac function indices showed that compared with the WKY, the LVSP increased significantly, the LVEDP decreased obviously, ±dp/dtmax was significantly increased in the WE; LVSP and ±dp/dtmax, although significantly increased in the SHR, the LVEDP was significantly higher than the WKY; compared with the SHR, the LVSP,LVEDP and ±dp/dtmax were decreased in the SE. The SE LVSP and LVEDP and decrease tends to the normal control group. These results show that cardiac function damage in the SHR. Long-term aerobic exercise can significantly improve cardiac function.4) Western blot results showed that compared with the WKY, LC3-?/LC3-? ratio, LC3-? and Beclinl protein expression was significantly increased in the WKY, the SHR was significantly decreased. Compared with the SHR, the SE was significantly higher; compared with the WKY, the expression of p62 in myocardium of the WE was significantly lower, and the SHR was significantly higher; compared with the SHR, the SE was significantly decreased. These results suggest that the level of autophagy in the myocardium of spontaneously hypertensive rats was decreased. Long-term aerobic exercise can improve the level of autophagy in spontaneously hypertensive rats.5) qRT-PCR results showed that LC3 mRNA expression levels changed in each group, but there is no significant difference between the groups. Compared with the WKY, the expression of mRNA p62 in myocardium of the WE was significantly decreased, and the expression of mRNA p62 in myocardium of the SHR was significantly increased; compared with the SHR, the expression of mRNA p62 in myocardium of the SE was significantly decreased. Compared with the WKY, The expression of mRNA Beclinl in myocardium of the WE was significantly increased, and the expression of mRNA Beclinl in myocardium of the SHR was significantly decreased. Compared with the SHR, The expression of mRNA Beclinl in myocardium of the SE was significantly increased. These results suggest that long-term aerobic exercise can change the expression of autophagy related gene mRNA in hypertensive rats. The effect of exercise on the level of autophagy related protein mRNA was consistent with the level of protein expression.Conclusion:1 In spontaneously hypertensive rats, the myocardial structure was damaged, the cardiac function decreased, and the level of autophagy decreased. The ratio of LC3-?/LC3-? and the expression of LC3-? has decreased. The expression of Beclinl and its mRNA level has decreased, and the expression of p62 and its mRNA level has increased.2 Long-term aerobic exercise can increase the level of autophagy and improve the structure and function of the myocardium in the myocardium of spontaneously hypertensive rats.