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Aims To observe the effects of trimetazidine, aerobic exercise alone or combined on the anti-stress capacity of mice, and further explore its potential mechanism. Methods Forty-four C57/BL male mice aged 8 weeks were randomly divided into four groups: control group (group C, n=11), exercise group (group E, n=11), trimetazidine (TMZ)group (group T, n=11),exercise combined with TMZ group (group TE, n=11). Saline intragastric administration, medium intensity swimming training, TMZ (10mg/kg) intragastric administration, medium intensity swimming training combined with TMZ intragastric administration were given respectively. Swimming for 6 days a week, 1 hour a day lasting for 4 weeks. After the intervention, each group was randomly subdivided into the rest and the exhaustive exercise (EE) subgroups. The mice in the EE-subgroup (n=6) underwent exhaustive exercise. The myocardial ultrastructure was observed under electron microscope to measure the anti-stress ability of mice. The expression of key autophagy proteins LC3-II, P62 and BNIP3 were detected and the number of myocardial autophagosomes were observed under electron microscope. The protein of apoptosis related, Bcl-2 and the expression of heat shock protein 70 (HSP70) were also being detected. Results Exhaustive exercise induced the cardiac muscle damage successfully. TMZ and exercise alone or combined alleviated the cardiac damage significantly with improved autophagy (P&amp;lt;0.05) at the basal state and after exhaustive exercise. The level of apoptosis (P&amp;lt;0.05) and the expression of HSP70 was upregulated after the exhaustive exercise. Conclusions TMZ and exercise alone improved the anti-stress capacity of mice effectively and the combination has a synergistic effect. The mechanism may be related to the promotion of autophagy, apoptosis and HSP70 expression of myocardium. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): China natual science founding

Trimetazidine combined with exercise improves anti-stress capacity through enhancing autophagy and apoptosis of myocardium in mice