| Objective:To investigate the dynamic effects of treadmill running at different intensities on cardiac structure and function of rats,the correlation between the properties of cardiac hypertrophy and intensity induced by running,and its mechanisms.Methods:A total of 72 adult SD rats were randomly divided into Sedentary group(SED),Low-intensity running group(LIR),Medium-intensity running group(MIR)and High-intensity running group(HIR).The animals of SED were housed in cages,while the running groups were carried out treadmill running according to their respective exercise plan.All animals were examined at 1week,4 weeks,and 8weeks as follows:Staining methods including hematoxylin-eosin(HE),wheat germ agglutinin(WGA),and picric sirius red(PSR)were used to detect cardiac histomorphology and myocardial fibrosis;Echocardiography was performed to evaluate changes in cardiac structure(left ventricular cavity diameter and wall thickness)and function(ejection function,heart rate and cardiac output);ELISA was performed to assay levels of serum marker cardiac troponin(c Tn-I);and Western Blot was used to determine the protein levels of MEK,ERK1/2 and p-ERK1/2 in heart.Results:(1)After 1 week’s running training,there was no significant difference in heart mass index(HMI)between each exercise group and SED group.However,the cardiomyocyte cross-sectional area in HIR group(6495±1067μm~2)was significantly enlarged compared with LIR group(3717±834μm2),MIR group(3706±681μm2)and SED group(3227±496μm2),respectively.HMI in each exercise group(LIR group:3.1±0.3mg/g,MIR group:3.3±0.3mg/g,HIR group:3.5±0.2mg/g)was significantly higher than that in SED group(2.6±0.1mg/g)following 4 weeks’exercise training.Moreover,the cardiomyocyte cross-sectional area in each exercise group(LIR group:7704±2368μm~2,MIR group:7771±1592μm~2,HIR group:9050±2550μm~2)was significantly higher than that in SED group(4936±1565μm~2),respectively.HIR group was also significantly enlarged compared with LIR and MIR groups.After 8 weeks’exercise training,HMI in each exercise group(LIR group:2.9±0.1mg/g,MIR group:3.2±0.2mg/g,HIR group:3.4±0.2mg/g)was significantly higher than that in SED group(2.5±0.1mg/g).Furthermore,the cardiomyocyte cross-sectional area in each exercise group(LIR group:8055±2102μm~2,MIR group:8448±2704μm~2,HIR group:9825±2420μm~2)was significantly higher than that in SED group(6030±1385μm~2).HIR group was also significantly enlarged compared with LIR and MIR groups.These findings indicated that the degree of myocardial hypertrophy is positively correlated with exercise intensity and period.(2)After 1 week,4 weeks and 8 weeks of exercise,the myocardial structure of SED,LIR and MIR groups were normal.While the myocardial structure of HIR group began to occasionally rupture after 4 weeks’exercise.Furthermore,the cardiomyocytes showed swelling,and the muscle fiber obviously exhibited arrangement disorder or even fracture,obscure boundary and interstitial edema,and the cardiomyocyte nucleus were shallow and unclear after 8 weeks of exercise,which suggested the injury of the myocardium.After 1 week’s short-term endurance exercise,there was no significant difference in left ventricular collagen volume fraction(CVF)between each exercise group and SED group.Following 4weeks’exercise training,although there was no significant difference in CVF between each exercise group and SED group,CVF in HIR group(2.37±0.49%)showed a significant increase than that in LIR group(1.66±0.31%)and MIR group(1.72±0.34%).After 8 weeks’exercise training,the CVF in HIR group(2.95±0.46%)was significantly higher than that in SED group(1.98±0.18%).On the contrary,the CVF in MIR group(1.56±0.25%)was significantly lower than that in SED group(1.98±0.18%).These findings showed that long-term medium-intensity exercise decreases myocardial interstitial fibrosis,and long-term high-intensity exercise increases myocardial interstitial fibrosis.(3)After 1 week’s exercise training,left ventricular end-diastolic diameter(LVEDD)(LIR group:7.495±0.48mm,MIR group:7.628±0.677mm),left ventricular end-systolic diameter(LVESD)(LIR group:4.46±0.576mm,MIR group:4.285±0.701mm),left ventricular end-diastolic volume(LVEDV)(LIR group:0.942±0.168ml,MIR group:0.998±0.219ml),and left ventricular end-systolic volume(LVESV)(LIR group:0.225±0.790ml,MIR group:0.207±0.890ml)were significantly higher than that in SED group(LVEDD:6.493±0.979mm,LVESD:3.070±0.814mm,LVEDV:0.657±0.222ml,LVESV:0.085±0.062ml).Left ventricular posterior wall thickness(LVPWT)in LIR group(1.767±0.137mm)and MIR group(1.750±0.164mm)were significantly lower than that in SED group(2.000±0.37mm),and cardiac output(CO)in MIR group(354.382±30.831ml)significantly higher than that in SED group(251.675±83.315ml).However,there was no significant difference in cardiac structure and function parameters between HIR group and SED group.After 4weeks’exercise training,LVEDV in MIR group(0.96±0.113ml)increased significantly compared with SED group(0.707±0.25ml),while the other parameters in each group were not significantly different from those in SED group.But CO in HIR group(166.91±54.841ml)was significantly lower than that in LIR group(263.764±46.099ml)and MIR group(266.84±44.624ml);Following 8weeks’exercise training,LVEDD in LIR group(7.117±0.624mm)and MIR group(7.202±0.635mm)significantly increased compared with SED group(6.458±0.761mm),and CO in LIR group(288.195±679.43ml)significantly higher CO than that in SED group(203.713±69.378ml).These findings suggested that endurance exercise training with different intensity has more considerable effect on ventricular expansion than wall thickening.(4)After 1 week’s exercise training,the levels of c Tn I in each exercise group was not different compared with SED group.After 4 weeks’exercise training,the levels of c Tn I in each exercise group(LIR group:483±207pg/ml,MIR group:555±216pg/ml,HIR group:500±167pg/ml)was significantly lower than those in SED group(1007±277pg/ml).After 8 weeks’exercise training,although the levels of c Tn I in LIR group(559±176pg/ml)and MIR group(460±117pg/ml)were still significantly lower than those in SED group(977±351pg/ml),there was no difference of the levels of c Tn I between HIR group and SED group.These findings revealed that the myocardial hypertrophy induced by endurance exercise training of different intensities is physiological.(5)One week’s exercise training slightly enhanced p-ERK protein expression in LIR and MIR groups without statistical difference,while that in HIR group(1.723±0.335)significantly upregulated compared with LIR group(1.100±0.171),MIR group(1.157±0.237)and SED group(0.843±0.074),respectively.After 4weeks’exercise training,the protein expression of p-ERK in each exercise group(LIR group:0.820±0.066,MIR group:0.830±0.095,HIR group:1.177±0.279)significantly upregulated compared with SED group(0.350±0.123).Meanwhile,the p-ERK protein expression in HIR group was also higher than that in LIR and MIR groups.After 8 weeks’exercise training,the expression of p-ERK protein in each exercise group was not different compared with SED group.These findings indicated that the ERK signaling pathway is not only associated with endurance exercise-induced cardiac hypertrophy,but also positively correlated with exercise loading,whereas long-term endurance exercise attenuates ERK signaling pathway activation.Conclusion:(1)Endurance exercise may lead to cardiac hypertrophy in an intensity-dependent manner.Long-term low and medium-intensity endurance exercise-induced cardiac hypertrophy should be physiological,whereas long-term high-intensity endurance exercise-induced cardiac hypertrophy is characterized by a pathological injury,which increases the risk of pathological development;(2)Endurance exercise training with different intensity has more obvious effect on ventricular expansion;(3)ERK signaling pathway is mainly involved in the compensatory hypertrophy process of the myocardium in the early stage of endurance exercise and is positively correlated with exercise loading.Long-term endurance exercise may attenuate ERK signaling activation. |
PDF Full Text Request