Trimetazidine Attenuates Exhaustive Exercise-Induced Myocardial Injury in Rats via Regulation of the Nrf2/NF-κB Signaling Pathway

Objective. To investigate whether exercise preconditioning (EP) protects the rat heart from exhaustive exercise- (EE-) induced injury by inducing the PI3K-Akt signaling pathway. Methods. 84 male Sprague-Dawley rats were randomly divided into 6 groups (n = 14 rats per group): control group (Con), exhaustive exercise group (EE), exercise preconditioning group (EP), exercise preconditioning + exhaustive exercise group (EP + EE), LY294002 (PI3K inhibitor) + exercise preconditioning + exhaustive exercise group (LY + EP + EE), and LY294002 group (LY). The Con and LY did not exercise. The remaining groups were subjected to treadmill running. The structure of myocardial tissue and serum biomarkers of myocardial injury were observed. Hemodynamic parameters were recorded with a pressure-volume catheter. TUNEL assay was used to detect the apoptosis of cardiac myocytes, and the level of mitochondrial membrane permeability transforming pore (mPTP) in myocardium was evaluated using ELISA. Pathway and apoptosis-related proteins in myocardium were assessed using western blotting. Results. Compared to the Con group, the EE group showed remarkable myocardial injury, such as cardiac dysfunction and myocardial apoptosis. Compared to the EE group, the injuries in the EP + EE group were improved. EP increased the PI3K-Akt signaling pathway and regulated Bcl-2 family to decrease the mPTP openness level. However, the cardioprotective effects of EP were attenuated when pretreated with the LY294002. Conclusions. EP protected the heart from EE-induced injury, and it may improve the cardiac function and reduce the cardiomyocyte apoptosis by activating the PI3K-Akt signaling pathway.

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Late Exercise Preconditioning Promotes Autophagy against Exhaustive Exercise-Induced Myocardial Injury through the Activation of the AMPK-mTOR-ULK1 Pathway

BioMed Research International ◽

10.1155/2019/5697380 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Hong-Tao Liu ◽

Shan-Shan Pan

Keyword(s):

Myocardial Protection ◽

Myocardial Injury ◽

Troponin I ◽

Picric Acid ◽

Exhaustive Exercise ◽

Class Iii ◽

Hypoxic Injury ◽

Exercise Preconditioning ◽

Exercise Induced ◽

The Relationship

Accumulating evidence shows that the AMPK-mTOR pathway modulates autophagy via coordinated phosphorylation of ULK1. The aim of the present study was to investigate the relationship between AMPK, mTOR, and ULK1 during late exercise preconditioning (LEP), and to explore whether LEP-induced myocardial protection is related to the autophagy. The exercise preconditioning (EP) protocol was as follows: rats were instructed to for run four repeated in duration of 10 minutes (including 10 minutes rest between each period) on a treadmill. Exhaustive exercise (EE) after LEP pretreatment and administration of wortmannin (an autophagy inhibitor that suppresses Class III PI3K-kinase (PI3KC3) activity) were added to test the protective effect. Cardiac troponin I (cTnI), and transmission electron microscopy (TEM), along with hematoxylin-basic fuchsin-picric acid (HBFP) staining, were used to evaluate the myocardial ischemic-hypoxic injury and protection. Western blot was used to analyze the relationship of autophagy-associated proteins. Exhaustive exercise caused severe myocardial ischemic-hypoxic injury, which led to an increase in cTnI levels, changes of ischemia–hypoxia, and cells ultrastructure. Compared with the EE group, LEP significantly suppressed exhaustive exercise-induced myocardial injury. However, wortmannin attenuated LEP-induced myocardial protection by inhibiting autophagy. Compared with the C group, AMPK was increased in the LEP, EE, and LEP+EE groups, but phosphorylation of AMPK at Thr172 was not significantly changed. Exercise did not have any effect on mTOR expression. Compared with the C group, ULK1 was increased and the ULK1ser757/ULK1 ratio was decreased in the LEP and LEP+EE groups. ULK1 was not significantly affected in the EE group, however, phosphorylation of ULK1 at Ser757 was remarkably decreased. To sum up, our results suggested that LEP promoted autophagy through the activation of AMPK-mTOR-ULK1 pathway, and that activated autophagy was partially involved in myocardial protection against EE-induced myocardial ischemic-hypoxic injury.

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