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

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.

Trimetazidine and exercise offer analogous improvements to the skeletal muscle insulin resistance of mice through Nrf2 signaling

“…The HFD+EX group was subjected to moderate-intensity swim training. 24 In brief, an adaptive training protocol was employed; mice were placed in a Morris water maze pool (XR-XM101-R, ZSdichuang, Beijing, China, with a diameter of 120 cm and a depth of 60 cm) and swam for 10 min on the first day. Thereafter, this was increased 10 min daily until 60 min/day.…”

Exercise‐mediated autophagy in cardiovascular diseases

“…35 Long-term exercise instigates benign changes in cardiac muscle autophagy and thus delays pathological remodeling to protect myocardial structure and function. By pre-implemented 5 weeks of aerobic exercise training on myocardial ischemia-reperfusion mice, Jiang et al 36 showed that exercise alleviated myocardial injury caused by ischemia-reperfusion and increased the expression of autophagy-related proteins BNIP3, LC3-II, and heat shock protein HSP70. These data indicated that exercise increased myocardial autophagy levels and enhanced the anti-stress capacity of mice.…”

Rhodiola pre-conditioning reduces exhaustive exercise-induced myocardial injury of insulin resistant mice

“…For IR or diabetic patients, the survival rate and prognosis of acute stress including myocardial infarction, are poor 1 , 2 , which indicates that cardiac anti-stress capacity is impaired by IR. In our previous research, we found that autophagy, heat shock protein 70 (HSP70), and mitochondrial quality control were found to be vital in anti-fatal stress capacity in healthy mice 3 – 5 .…”