| Object:To investigating the effect of exercise on Wnt/NRG1 pathway in heart with myocardial infarction (MI) and the differences of myocardial and skeletal muscle NRGl expression in different gender with resistance training; Providing experimental evidence for the prevention and treatment of human heart disease.Materials and Methods:72 male and 36 female 3-month-old SD rats were fed with the national standard rodent dry feed in a week.12 male and 12 female rats were selected randomly as sham group(S) and female sham group(FS), respectively. Meanwhile the rest rats were operated with left anterior descending (LAD) ligation surgery.All the rats with surgery were divided randomly into 7 groups:myocardial infarction group (MI), female MI group(FMI), Ml+resistance training group (MMR), female MI+resistance training group (MMR),MI+aerobic training group(ME),MI+high-intensity interval aerobic exercise group (MA), MI+intermittent mechanical vibration group (MV).4-week Rat resistance training(MR and FMR):Start the training a week after operation.The height of ladder is 1.1 m, the ladder spacing is 2 cm and the angle of inclination is 85°. One-week adaptive training started with no load, progressed with a daily increment of 10% weight load, ended with 75% weight load.4-week Rat aerobic exercise(ME):The training begun a week after operation.After one-week adaptive training with lOm/min,30min/day treadmill running,4-week treadmill running started with 40%-50% Vo2max warm-up and lOm/min of treadmill speed 10 minutes,then speed up to 16 m/min 50 minutes,5d/week training in 4 weeks.4-week Rat intermittent aerobic exercise(MA):The training begun a week after operation. The first week of adaptive training proceeded in the speed of 10m/min and lasted 30min; the one-hour formal training consisted of three parts of alternating exercise:10 min of warm-up in the speed of 1 Om/min,7 min of exercise in the speed of 25m/min (exercise intensity 85%-90% VO2max),3 min of exercise in the speed of 15m/min (exercise intensity 50%-60% VO2max), and 5-day training a week.4-week vibration training(MV):7 days after operation,one-week adaptive vibration training proceeded in the frequency of 15HZ,15min/time, ltime/d,5d/wk; From the second week, formal vibration training proceeded in the frequency of 25HZ, amplitude of 2mm, time of 15min,2time/d, intermittent of 8min, the total training time is 38min,5days/week, lasted 4wks.Using PowerLab 8/30 bio-signal analysis system to measure hemodynamics, heart rate and ECG indicators; Using paraffin sections, Masson staining, HE staining and morphological parameters to measure the heart and skeletal muscles; Using immunofluorescence and Western Blot method to observe and determine protein expression of Wnt3a、β-catenin、LEF1、DKK1 in the myocardium, the protein expression of NRG1 and ErbB2/4 in the both heart and skeletal muscles.Results:(1) A large number of myocardial collagen hyperplasia was in myocardium of MI rats. Alternative fibrosis was visible significantly, which extended to the edge area of infarction and non-infarction. Collagen volume fraction (CVF%) was reduced differently by resistance training, continuous aerobic exercise, intermittent aerobic exercise and mechanical vibration training. There was a certain extent difference of different exercise modes. CVF% could be declined significantly by intermittent aerobic exercise.(2) Highly raised heart coefficient, HR and LVEDP were accompanied by significantly declined LVSP and ±dp/dtmax in MI rats suggested that MI seriously damaged the heart function. Heart function of MI rats was improved by resistance training, continuous aerobic exercise, intermittent aerobic exercise and mechanical vibration training. There was a certain extent difference of different exercise modes. Heart function could be improved mostly by resistance training and intermittent aerobic exercise.(3) Cardiomyocytes apoptosis occurred in MI rats. The number of apoptotic cardiomyocytes was reduced differently by resistance training, continuous aerobic exercise, intermittent aerobic exercise and mechanical vibration training. There was a certain extent difference of different exercise modes without significance.(4) Death rate of MI rat model was about 8.3%. The death rate of resistance training, continuous aerobic exercise, intermittent aerobic exercise and mechanical vibration training were 8.3%,16.7%,25% and 0%, respectively. The death rate of intermittent aerobic exercise group was the highest. Comprehensive analysis showed that intermittent aerobic exercise had the best of efficient on heart function improvement with the highest risk. Resistance training had relatively high efficacy and safety.(5) Continuous aerobic exercise and mechanical vibration training could slightly up-regulate NRG1 expression in infarction myocardium without significance. Resistance training and intermittent aerobic exercise could up-regulate NRG1 expression obviously. This result suggested that different exercise modes increased NRG1 expression in infarction myocardium on different level.(6) The intervention of resistance training, continuous aerobic exercise and intermittent aerobic exercise increased ErbB2/4 expression in myocardium. The intervention of mechanical vibration training could obviously increase ErbB2 but not ErbB4 expression in myocardium. There was much difference in several exercise modes such as resistance training, continuous aerobic exercise, intermittent aerobic exercise and mechanical vibration training. It suggested that myocardium ErbB2/4 expression was raised by exercise, and changed by exercise mode.(7) The expression of Wnt3a, β-catenin and LEF1 protein were increased markedly, while DK.K1 expression was decreased markedly by resistance training, continuous aerobic exercise, intermittent aerobic exercise and mechanical vibration training. Various modes of exercise could activate Wnt pathway, up-regulate Wnt related protein. Comprehensive analysis showed that various modes of exercise improved the expression of NRG1 and its receptor ErbB2/4, activated Wnt pathway. Resistance training and intermittent aerobic exercise had more significant effect of NRG1/ErbB2/4 and Wnt/β-catenin activation.(8) Resistance training had auxo-action on the heart function improvement. Male was significantly higher than female. Gender difference was existence. Resistance training could degrade cardiac collagen fiber hyperplasia in MI heart of male and female rats without significance. Gender difference was inexistence.(9) Skeletal muscle mass, myocyte cross-sectional area, NRG1 and ErbB2/4 expression in skeletal muscle were increased by resistance training. Male was significantly higher than female. Gender difference was existence.(10) NRG1 and ErbB2/4 expression were markedly increased in myocardium of male and female rats. There was no notable gender difference.Conclusion:Resistance training、high-intensity interval aerobic exercise、aerobic exercise and vibration training can reduced the CVF percent, while significantly improve the cardiac function in MI rats. Among the different exercise training forms, High-intensity interval aerobic exercise is most effective in rebuilding the cardiac structure and improving the heart function, but it is also with high risk. Resistance training is proved to be both efficient and safe. Although all the exercise forms can activate the Wnt-NRG1-ErbB2/4 pathway in MI heart, the resistance training and high-intensity interval aerobic exercise have the more significant effect on the motivation.Resistance training can effectively improve cardiac function and structure in MI rats, and significantly up-regulate the expression of NRG1 and its own receptors ErbB2/ErbB4 in the MI heart and skeletal muscle, which may contribute to the increase of skeletal muscle mass and myocyte cross-sectional area after MI. Besides, the effects of resistance training vary from the different genders,the male rats benefit more from the resistance training than the females. |
PDF Full Text Request