Int J Med Sci 2021; 18(7):1680-1686. doi:10.7150/ijms.53899

Research Paper

Exercise combined with trimetazidine improves anti-fatal stress capacity through enhancing autophagy and heat shock protein 70 of myocardium in mice

Lingjun Jiang1,3*, Xuanlin Shen2*, Yaoshan Dun1, Murong Xie1, Siqian Fu1, Wenliang Zhang1, Ling Qiu1, Jeffrey W. Ripley-Gonzalez1, Suixin Liu1✉

1. Division of Cardiac Rehabilitation, Department of Physical Medicine & Rehabilitation, Xiangya Hospital Central South University, Changsha, Hunan 410008, P.R China.
2. Department of Rehabilitation, The Affiliated Changshu Hospital of Xuzhou Medical University, Changshu, Jiangsu 215500, P.R China.
3. Division of Sport and Rehabilitation Medicine, University Hospital Ulm, Parkstr. 11, 89075, Ulm, Germany.
*These authors contributed equally to this study.

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Citation:
Jiang L, Shen X, Dun Y, Xie M, Fu S, Zhang W, Qiu L, Ripley-Gonzalez JW, Liu S. Exercise combined with trimetazidine improves anti-fatal stress capacity through enhancing autophagy and heat shock protein 70 of myocardium in mice. Int J Med Sci 2021; 18(7):1680-1686. doi:10.7150/ijms.53899. Available from https://www.medsci.org/v18p1680.htm

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Abstract

Background: Anti-stress capacity is important to resist the occurrence of adverse events. To observe the effects of exercise, trimetazidine alone or combined on the anti-stress capacity of mice, and further explore its potential mechanism.

Methods: Forty-four C57BL/6 male mice aged 8 weeks were randomly divided into four groups (n=11 for each group): control group (group C), exercise group (group E), trimetazidine group (group T), exercise combined with trimetazidine group (group TE). After the intervention, each group was randomly subdivided into the exhaustive exercise (EE, n=6) and the non-EE (n=5) subgroups. The mice in the EE-subgroup underwent EE. Mice were sacrificed 12 hours later after EE. The myocardial ultrastructure and autophagosomes were observed under an electron microscope. The expression of autophagy-related proteins: BNIP3, LC3-II, and P62 were analyzed and the heat shock protein 70 mRNA transcription and protein expression were also investigated.

Results: Exercise or trimetazidine increased the expression of BNIP3, LC3-II, and heat shock protein 70, decreased the expression of P62 pre- and post-EE while the combination has the synergistic effect.

Conclusion: Exercise and trimetazidine, alone or combined enhanced the anti-stress capacity of mice significantly. The underlying mechanism may be associated with the promotion of autography and the expression of heat shock protein 70.

Keywords: anti-stress capacity, Trimetazidine, exercise, autophagy, heat shock protein 70