| Objective: To establish an animal model of chronic heart failure(CHF)by intraperitoneal injection of Doxorubicin hydrochloride(DOX),and to explore the effects of perindopril combined with moderate-intensity continuous exercise on adriamycin-induced chronic heart failure in mice The role and mechanism.Method: Ninety male C57 mice were randomly divided into two groups:doxorubicin hydrochloride group(DOX group)(n=78,intraperitoneal injection of doxorubicin hydrochloride 2mg/kg,first 4 times,once every other day,after 6 One time/w,a total of 7w,a cumulative dose of 20mg/kg),a blank control group(CON group)(n=12,injected with the same amount of normal saline through the same route)to prepare a CHF animal model.After 7 weeks of intraperitoneal injection,drug withdrawal was observed for 2 weeks,echocardiography was used to check the cardiac function of mice,and plasma BNP was detected by ELISA.Finally,the ventricular muscle tissue was taken for HE staining to observe the degree of myocardial injury.After the model building was successful,the model mice were randomly divided into distilled water gavage group(n=12,pre-distilled water gavage for 4w),and perindopril group(n=12,perindopril 2mg/kg/ d gavage,a total of 4w),perindopril + exercise group(n=12,give perindopril 2mg/kg/d gavage,while giving a speed of 14m/min,60min/d,6 times/w,A total of 4 weeks of moderate-intensity exercise),48 hours after the end of the last exercise,anesthesia was performed under echocardiography to check the cardiac function of the mouse,and then the blood was drawn from the internal canthus vein for ELISA to detect plasma BNP and inflammation indicators IL-10 and IL-1β,and finally executed In mice,the oxidative stress indexes SOD and MDA of myocardial tissue were detected by biochemical method,and HE staining of ventricular muscle tissue was used to observe the degree of myocardial injury in mice of each group.Result:1.The results of echocardiographic examination showed that compared with the CON group,the left ventricular end systolic diameter(LVIDs)and left ventricular end diastolic inner diameter(LVIDd)of mice in the distilled water intragastric group were increased(P<0.05),and left ventricular ejection fraction(LVEF),decreased left ventricular short axis shortening rate(LVFS)(P<0.05),which indicates that there is severe left ventricular dysfunction in mice;compared with distilled water gavage group,perindopril group,perindopril + In the exercise group,the left ventricular end-diastolic diameter(LVIDd)and left ventricular endsystolic diameter(LVIDs)decreased(P<0.05),and left ventricular ejection fraction(LVEF)increased(P<0.05),indicating that perindopril alone The combined exercise training of perindopril and perindopril helps to improve the ventricular remodeling induced by doxorubicin;compared with the perindopril group,the left ventricular end systolic diameter(LVIDs)and left ventricle of the perindopril + exercise group mice Decreased end-diastolic diameter(LVIDd)(P<0.05);increased left ventricular ejection fraction(LVEF)and left ventricular short-axis shortening rate(LVFS)(P<0.05),indicating that perindopril combined with exercise training improved Azerbaijan The ventricular remodeling induced by Amycin is better than the improvement effect of perindopril alone.2.ELISA test results of mouse plasma show:(1)Compared with the CON group,the plasma BNP in the distilled water gavage group,perindopril group,and perindopril + exercise group increased(P<0.05);compared with the distilled water gavage group,the perindopril group,culture Plasma BNP decreased in the indopril + exercise group(P<0.05);and the plasma BNP decreased more significantly in the perindopril + exercise group than in the perindopril group(P<0.05).(2)Compared with the CON group,the plasma IL-1β level in the distilled water gavage group,perindopril group,and perindopril + exercise group increased(P<0.05);compared with the distilled water gavage group,perindopril Plasma IL-1β level in group and perindopril + exercise group decreased(P<0.05),and IL-1βdecreased more significantly in perindopril + exercise group than in perindopril group(P<0.05).(3)Compared with the CON group,the plasma IL-10 level in the distilled water gavage group,perindopril group,and perindopril + exercise group increased(P<0.05);compared with the distilled water gavage group,perindopril Plasma IL-10 level in group and perindopril + exercise group decreased(P<0.05);and IL-10 decreased more significantly in perindopril + exercise group than perindopril group(P<0.05).3.The biochemical test results of mouse myocardial tissue show:(1)Compared with the CON group,the SOD activity of the distilled water gavage group and the perindopril group decreased(P<0.05),while the SOD activity of the perindopril + exercise group showed no significant difference compared with the CON group(P>0.05);Compared with the distilled water gavage group,the SOD activity of the perindopril group and perindopril +exercise group increased(P<0.05),and the SOD activity of the perindopril +exercise group was more obvious than that of the perindopril group.(P<0.05).(2)Compared with the CON group,the MDA content of the distilled water gavage group and the perindopril group increased(P<0.05),while the MDA content of the perindopril + exercise group showed no significant difference compared with the CON group(P>0.05);Compared with the distilled water gavage group,the MDA content of the perindopril group and perindopril +exercise group decreased(P<0.05),and the MDA content of the perindopril +exercise group was more significantly decreased than that of the perindopril group(P<0.05).4.HE staining results show:In the blank control group,the texture of myocardial tissue was clear,the shape of myocardium was regular,and it was banded.The myocardial cells were arranged in parallel and regular without breakage and disappearance.The myocardial cell nucleus was located in the center of the cell,and there was no necrosis and disappearance of the nuclear cell.In the distilled water gavage group,the myocardial cell nucleus liquefaction,necrosis or disappearance,myocardial cell edema and degeneration,partly showed small focus and flake necrosis,myocardial fiber arrangement disordered,broken and disappeared to varying degrees,the myocardial cell gap was significantly widened,and inflammation was seen Infiltration of cells.In the perindopril group,the arrangement of myocardial fibers was disordered,and some of the myocardial fibers were broken and disappeared.The edema and degeneration of myocardial cells were reduced compared with the distilled water group,and a small amount of infiltration of inflammatory cells was seen.In the perindopril + exercise group,the myocardial fiber arrangement disorder,myocardial cell edema and degeneration were significantly reduced compared with the distilled water intragastric group and the perindopril group.Conclusion:1.Perindopril combined with exercise training can improve the cardiac function and exercise ability of mice with chronic heart failure induced by doxorubicin.2.Perindopril combined with exercise training can reduce the plasma BNP,IL-1β,IL-10 of mice with adriamycin-induced chronic heart failure,which shows that perindopril combined with exercise training can improve adriamycin-induced chronic heart failure.Mouse humoral factors activate and regulate antiinflammatory cytokines and pro-inflammatory cytokines,thereby reducing inflammation.3.Perindopril combined exercise training can increase the antioxidant enzyme SOD activity of adriamycin-induced chronic heart failure mice,and reduce the content of lipid peroxidation MDA,which shows that perindopril combined exercise training can regulate antioxidant enzymes and lipid peroxidation,reduce oxidative stress.4.Perindopril combined with exercise training can improve the myocardial structure changes of mice with chronic heart failure induced by doxorubicin.5.The combined effect of perindopril combined with exercise training on adriamycin-induced inflammation,oxidative stress,and myocardial structure improvement is partially better than that of perindopril alone,indicating that perindopril and exercise training are improving cardiac function.It has a synergistic effect on exercise ability,and further explains that the cardiac rehabilitation of patients with chronic heart failure should be based on drugs,supplemented by moderate exercise. |
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