Different Intensity Exercise Preconditions Affect Cardiac Function of Exhausted Rats through Regulating TXNIP/TRX/NF-ĸB_p65/NLRP3 Inflammatory Pathways

Abstract

Objective. To investigate whether exercise preconditioning (EP) improves the rat cardiac dysfunction induced by exhaustive exercise (EE) through regulating NOD-like receptor protein 3 (NLRP3) inflammatory pathways and to confirm which intensity of EP is better. Method. Ninety healthy male Sprague Dawley rats were randomly divided into five groups: a control group (CON), exhaustive exercise group (EE), low-, middle-, and high-intensity exercise precondition and exhaustive exercise group (LEP + EE, MEP + EE, HEP + EE group). We established the experimental model by referring to Bedford’s motion load standard to complete the experiment. Then, the pathological changes of the myocardium were observed under a light microscope. Biomarker of myocardial injury in serum and oxidative stress factor in myocardial tissue were evaluated by ELISAs. The cardiac function parameters were detected using a Millar pressure and volume catheter. The levels of thioredoxin-interacting protein (TXNIP), thioredoxin protein (TRX), nuclear transcription factor kappa Bp65 (NF-ĸBp65), NLRP3, and cysteinaspartate specific proteinase 1 (Caspase-1) protein in rats’ myocardium were detected by western blotting. Results. 1. The myocardial structures of three EP + EE groups were all improved compared with EE groups. 2. The levels of the creatine phosphating-enzyme MB (CK-MB), reactive oxygen species (ROS), interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α) in three EP + EE groups were all increased compared with CON but decreased compared with the EE group (P<0.05). 3. Compared with the CON group, slope of end-systolic pressure volume relationship (ESPVR), ejection fraction (EF), and peak rate of the increase in pressure (dP/dtmax) all dropped to the lowest level in the EE group (P<0.05), while the values of cardiac output (CO), stroke volume (SV), end-systolic volume (Ves), end-diastolic volume (Ved), and relaxation time constant (Tau) increased in the EE group (P<0.05). 4. Compared with the CON group, the expression levels of TXNIP, NF-ĸBp65, NLRP3, and Caspase-1 all increased obviously in the other groups (P<0.05); meanwhile, they were all decreased in three EP + EE groups compared with the EE group (P<0.05). 5. NLRP3 was positively correlated with heart rate, IL-6, and ROS, but negatively correlated with EF (P<0.01). Conclusion. EP protects the heart from EE-induced injury through downregulating TXNIP/TRX/NF-ĸBp65/NLRP3 inflammatory signaling pathways. Moderate intensity EP has the best protective effect.

Optimization of different intensities of exercise preconditioning in protecting exhausted exercise induced heart injury in rats

“…The serum marker analyses suggest that cTn-I and NT-proBNP were released into blood after exhaustive exercise, so the contents of these enzymes in the serum increased significantly, indicating that the cardiomyocytes were injured, which is in line with numerous studies on animals models 14 , 20 , 21 and human studies. 22 , 23 After EP, the contents of cTn-I and NT-proBNP in serum of exhausted rats were decreased, indicating that EP had the ability to resist the myocardial injury.…”

“… 13 EP down-regulates TXNIP/TRX/NF-ĸBp65/NLRP3 inflammatory signaling pathway, and reduces the content of downstream inflammatory factors. 14 …”

“…YM Li et al. 14 reported the moderate intensity EP(i.e., 32 m/min, at 65% -75% ˙O 2max ) had a better effect on regulating inflammatory pathways and protecting cardiac function. Studies have found that the activities of various myocardial mitochondrial complex enzymes were increased during moderate-intensity training, while low-intensity training modes had no significant effect on the activities of these complex enzymes.…”

Compositions and Functions of Mitochondria-Associated Endoplasmic Reticulum Membranes and Their Contribution to Cardioprotection by Exercise Preconditioning

“…Although acute exercise increased the expression of thioredoxin-interacting protein (TXNIP), nuclear transcription factor kappa B p65 (NF-κB P65 ), NLRP3, and Caspase-1, EP at different intensities protected the heart from EE-induced injury by downregulating the TXNIP/thioredoxin protein (TRX)/NF-κB P65 /NLRP3 inflammatory signaling. EP at moderate intensities had the best protective effect ( Li et al, 2020b ). Exercise also may exert cardioprotective effects by modulating GRP78.…”

Research Progress of Mitochondrial Mechanism in NLRP3 Inflammasome Activation and Exercise Regulation of NLRP3 Inflammasome

“…These above results indicate that moderate exercise benefits the immune system. Additionally, exercise preconditioning were also shown to protect against the NLRP3 inflammasome overactivation induced by acute exercise [ 73 ].…”