Experimental Study On The Effects Of Aerobic Exercise On Cardiac Function And Myocardial Fibrosis In Pressure Overload Mice

Purpose: With the long-term overloaded pressure,hypertension will cause the reduction of cardiac function through its effect on myocardial interstitial fibrosis.The long-term aerobic exercise can improve the cardiac function,but whether the mechanism is related to its effect on improving myocardial fibrosis and whether the heat shock factor protein 1(HSF1)plays a regulating role in the aerobic exercise remain unknown.The study aims to find out the mechanism of how the long-term aerobic exercise acts on cardiac function and myocardial fibrosis in mice with hypertension,thus providing a research basis for the kinesitherapy of hypertension.Methods: Surgery of aortic coarctation was adopted to mimic the model of hypertension.Male balb/c mice,8-week years old,60 in total,were divided into three groups(n=20 per group),namely the control group(CON),the surgery group(TAC),and surgery plus exercise group(TAE)respectively.Groups of TAC and TAE underwent the transverse aortic constriction(TAC)to build the model of hypertension.Group of TAC underwent a ten-week aerobic exercise of treadmill running four days after the surgery.Mice in the group of TAE underwent zero-slop treadmill running.Progressive increasing exercise running schedule was adopted,increasing from 12meter/min plus 30 minutes in the first week to 15 meter/min plus 60 minutes in the fifth week,and keeping this rate to the end of the tenth week.After the ten-week exercise,Vevo770 diasonograph and 30 MHz high frequency probe were used to do the cardiac ultrasonic testing on mice of these three groups.Left ventricular internal dimension systole(LVIDs),left ventricular internal dimension diastole(LVIDd),left ventricular ejection fraction(EF%)and Heart rate(HR)were measured.The millar conduit was used for hemodynamics analysis to measure the right neck aortic pressure.Mice were first sampled,and then their hearts were weighted immediately to calculate the ratio of heart to body.Pathological staining of HE and masson was used to observe the degree of myocardial hypertrophy and myocardial fibrosis.Quantitative real-time PCR was used to measure the m RNA expression of Heat shock transcriptionfactor 1(HSF1).Results: Mice were in good condition during the experimental process.Their body weights grow steadily.The pressure-measuring result of the main artery shows:Compared with CON group,the blood pressure of TAC group increased about50 mmHg.After the 10-week aerobic exercise,the blood pressure(P<0.05)of TAE group decreased apparently.As the ultrasonic cardiogram read,the LVEF of mice in TAC group was lower(P<0.05),while the LVIDd and the LVIDs was higher(P<0.01)than that of CON group.The LVEF of mice in TAE group was higher(P<0.05),while the LVIDd and LVIDs was lower(P<0.01)than that of TAC group.The weight ratio of heart to body was higher in mice of TAC group compared to that of the mice in CON group,which decreased after exercise.As the HE staining showed,mice in TAC group had more cellular hypertrophy than CON group,while exercise could decrease cross-sectional area in cardiomyocytes.As the Masson staining showed,the myocardial fibrosis in TAC group was apparently more than that in CON group,and that in TAE group was less than that in TAC group.Seen from the HSF1 expression,mice in TAC group was lower(P<0.01)than CON group,while mice in TAE group was higher(P<0.01)than TAC group obviously.Conclusions:1.It is feasible to build the animal model of over-loaded pressure through transverse aortic constriction and the model of aerobic exercise after surgery.2.Ten-week hypertension could induce myocardial hypertrophy and myocardial fibrosis,thus leading to reduction in cardiac function.Aerobic exercise could alleviate the reduction of cardiac function and the degree of myocardial fibrosis.3.Over-load hypertension contributed to reduction of HSF1 in cardiac tissue.Aerobic exercise could protect heart from myocardial injury through alleviating myocardial fibrosis caused by hypertension,and the mechanism might correlate with increased expression of HSF1 in cardiac tissue.