Netrin-1 plays a role in the effect of 10 weeks moderate exercise on myocardial fibrosis in rats

Abstract

This study aimed to determine the effect of Netrin-1 and its receptor on acute 13 myocardial infarction in rats after aerobic exercise.METHODS:Twenty-four rats were randomly 14 divided into three groups: the sham group (n = 8); acute myocardial infarction model group 15 (AMI)(n = 8); and aerobic exercise treatment after acute myocardial infarction group(ET) (n = 8). 16 After 10 weeks, the levels of netrin-1, tumor necrosis factor alpha α(TNF-α), and interleukin 6(IL-6) 17 in the serum were measured. The expression of matrix metalloproteinases 2 and 9(MMP2,9), and 18 their inhibitor, tissue inhibitor of metalloproteinases 2(TIMP2), myocardial netrin-1, Deleted in 19 colorectal cancer(DCC) receptor were evaluated. Histopathological were evaluated. The collagen 20 volume fraction of myocardial tissues was also calculated.RESULTS:Compared to the sham 21 group, the AMI group and ET groups showed increased levels of serum TNF-α, IL-6 and 22 significantly reduced levels of netrin-1. Levels of TNF-α and IL-6 were significantly reduced in 23 the ET group compared to the AMI group, whereas the level of netrin-1 was increased. The 24 expression of myocardial MMP2,9 was significantly increased in the AMI group compared to the 25 sham group, whereas that of myocardial netrin-1, inhibitor of TIMP2 and DCC receptor , was 26 significantly reduced. Compared to AMI group, the ET group showed reduced expression of 27 myocardial MMP2,9 proteins, whereas expression of myocardial netrin-1, inhibitor of TIMP2 and 28 DCC receptor, was significantly increased. The collagen volume fraction of myocardial tissues 29 was significantly increased in the AMI group and ET group compared to the sham group, with the 30 greater increase being noted in the AMI group.CONCLUSIONS: Aerobic exercise could increase 31 levels of serum netrin-1 myocardial netrin-1, and DCC receptor and reduced expression of 32 myocardial MMP2,9 proteins, to improve the degree of fibrosis following myocardial infarction 33 in rats. 34 Keywords: netrin-1, acute myocardial infarction, aerobic exercise, rats 35 51 The role of netrin-1 in cardiovascular disease and the stages of acute inflammation is an 52 emerging area of research. Some studies have shown that an appropriate increase in the 53 concentration of netrin-1, can alleviate myocardial ischemia-reperfusion injury, and reduce 54 atherosclerosis (6, 7). Liu and others (8) reported that aerobic exercise could increase the 55 expression of netrin-1 to relieve cerebral reperfusion injury in rats. However, whether aerobic 56 exercise will show similar effects in myocardial cells has not yet been reported. 57 Therefore, the present study was undertaken to discuss the netrin-1 changes after 58 myocardial fibrosis, and evaluate the effect of aerobic exercise on netrin-1 after 59 myocardial infarction. 60 61 Materials and methods 62 Animals and groups 63 Healthy adult male Sprague Dawley (SD) rats, weighing 180-220 g were supplied by the Animal 64 Experiment Center of Harbin Medical University. The rats were randoml...