Study on the Improvement of Cardiac Function Through Reducing Myocardial Damage in Autistic Mice by Aerobic Exercise
Objective:To investigate the effect of aerobic exercise on improving the cardiac function of Valproic acid(VPA)-induced Autism spectrum disorder(ASD)mice.Methods:A total of 42 4-week-old C57/BL6 female and male mice were randomly divided into Control group(CTL),VPA-induced autism group(VPA)and VPA+aerobic Exercise group(VPE),with 7 mice in each group.A single intraperitoneal injection of VPA was performed on pregnant mice at embryo(E)12.5 to establish an autism mouse model.The male and female mice in the VPE group were subjected to aerobic exercise intervention for 8 weeks.After the exercise,behavioral tests including the open field experiment,the elevated cross maze experiment and the new object recognition experiment were conduc-ted.Cardiac function was measured by echocardiography.The activities of total antioxidant capacity(T-AOC),su-peroxide dismutase(SOD)and malondialdehyde(MDA)in myocardium and serum were detected by Elisa,which evaluated the antioxidant capacity of heart.Lactate dehydrogenase(LDH),brain natriuretic peptide(BNP),crea-tine kinase(CK)and creatine kinase isoenzyme(CKMB)activities were measured to evaluate cardiac injury.Car-diomyocyte apoptosis was detected of using TUNEL staining.Results:ASD mice of both genders showed significantly reduced free activity,increased anxiety,and significant cognitive deficits.After 8 weeks of aerobic ex-ercise intervention,the free activity of male and female mice increased significantly,anxiety and cognitive defects improved markedly(P＜0.01,P＜0.05),indicating that the model of autism was successfully created.Compared with the CTL group,the VPA group exhibited significantly decreased FS％and EF％(P＜0.01),significantly in-creased LVEDV,LVESV,LVIDd,LVIDs,and E/e'(P＜0.01),significantly decreased myocardial local and ser-um T-AOC and SOD(P＜0.01,P＜0.05),significantly increased MDA,LDH,BNP,CK,and CKMB(P＜0.01,P＜0.05),and significantly increased TUNEL-stained positive particles(P＜0.01).Compared with the VPA group,the VPE group showed significantly increased EF％and FS％(P＜0.01),significantly decreased LVEDV,LVESV,LVIDd,LVIDs,and E/e'(P＜0.01,P＜0.05),significantly upregulated myocardial local and serum T-AOC and SOD(P＜0.01,P＜0.05),significantly decreased MDA,LDH,BNP,CK,and CKMB(P＜0.01,P＜0.05),and significantly decreased TUNEL-stained positive particles(P＜0.01).Conclusion:ASD can seriously impair free activity and cognitive function,increase anxiety,impair myocardial antioxidant capacity,increase myo-cardial injury,and decrease cardiac function in male and female mice.Aerobic exercise intervention can improve myocardial antioxidant capacity,reduce myocardial injury,inhibit myocardial cell apoptosis,enhance cardiac func-tion,and improve ASD behaviors.It is speculated that alleviating myocardial oxidative stress injury and inhibiting cardiomyocyte apoptosis may be important targets for aerobic exercise to improve cardiac function in ASD.
aerobic exerciseautism spectrum disordermyocardial injurycardiac function
万方数据
维普
