Effects of aerobic interval training on myocardial oxidative stress and inflammation in rats with myocardial infarction and its mechanism

doi:10.12047/j.cjap.6094.2021.043

Abstract

Abstract: Objective: The present study was to determine the effects of aerobic interval training (AIT) on the expressions of SIRT1, Nox4 and inflammatory factor in the heart of rats with myocardial infarction (MI). Methods: Male Sprague Dawley rats were randomly divided into sham-operated group (C), sedentary MI group (MI) and MI with AIT group (ME) (n=10). The MI model was established by ligation the left anterior descending coronary artery. Rats in C groups were subjected to the same surgery, but only threaded and not ligated. After surgery 1 week, rats in ME groups took adaptability training for 1 week, and then subjected to 4 weeks treadmill exercise training. After training, the hearts were collected for histological observation. The level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in heart was assessed by ultraviolet spectrophotometry. The activity of lactate dehydrogenase (LDH) was determined by enzyme linked immunosorbent assay. The expression of sirtuin1 (SIRT1) mRNA was examined by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of SIRT1, NADPH oxidase 4 (Nox4), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were detected by Western blotting. The levels of reactive oxygen species (ROS) were detected by dihydroethidium (DHE) staining. Results: Compared with the C group, the expression level of cardiac Nox4 protein was increased (P＜0.01), the level of MDA, activity of LDH and the level of ROS were increased significantly (P＜0.01), and the expressions of TNF-α and IL-1β protein were augmented in the heart of rats with MI (P＜0.01). However, the expressions of SIRT1 mRNA and protein and the activity of SOD were obviously decreased in MI group (P＜0.01). Furthermore, compared with the MI group, AIT increased the expressions of SIRT1 mRNA and protein and the activity of SOD in the heart of ME group (P＜0.01); Meanwhile, the expressions of cardiac Nox4, MDA level, LDH activity and ROS level were diminished in ME group (P＜0.01) as well as the decreased expressions of TNF-α and IL-1β protein (P＜0.01). SIRT1 expression was negatively related to the expressions of NOX4 and ROS. Conclusion: AIT obviously inhibited myocardial oxidative stress and inflammatory reaction, improved cardiac function in rats with MI, and the mechanism was closely related to the activation of SIRT1-Nox4-ROS signaling pathway.

Key words: myocardial infarction, aerobic interval training, SIRT1, oxidative stress, inflammation, rats

CLC Number:

G804.5

GENG Yuan-wen, LIN Qin-qin, WANG Xiang-yi, LI Ruo-ming, TIAN Zhen-jun. Effects of aerobic interval training on myocardial oxidative stress and inflammation in rats with myocardial infarction and its mechanism[J]. CJAP, 2021, 37(4): 439-444.

References 20

[1]	蒋易, 燕艳丽, 白建文. 抗细胞趋化因子CCL21单克隆抗体处理对小鼠急性心肌梗死后左心室重构及心功能的影响[J]. 中国应用生理学杂志, 2018, 34(3): 197-200.
[2]	Liao J, Yang X, Lin Q, et al. Inhibition of the Ubiquitin-activating enzyme UBA1 suppresses diet-induced atherosclerosis in apolipoprotein E-knockout mice [J]. J Immunol Res, 2020, 2020: 7812709.
[3]	Ranjbar K, Nazem F, Nazari A. Effect of exercise training and L-arginine on oxidative stress and left ventricular function in the post-ischemic failing rat heart [J]. Cardiovasc Toxicol, 2016, 16(2): 122-129.
[4]	Ding S, Liu D, Wang L, et al. Inhibiting microRNA-29a protects myocardial ischemia-reperfusion injury by targeting SIRT1 and suppressing oxidative stress and NLRP3-mediated pyroptosis pathway [J]. J Pharmacol Exp Ther, 2020, 372(1): 128-135.
[5]	Chan SH, Hung CH, Shih JY, et al. Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling [J]. Redox Biol, 2018, 14: 116-125.
[6]	Wisloff U, Loennechen JP, Currie S, et al. Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility, Ca2+ sensitivity and SERCA-2 in rat after myocardial infarction [J]. Cardiovasc Res, 2002, 54(1): 162-174.
[7]	叶挺梅, 张世忠, 夏强. 线粒体钙单向转运体在心肌低氧/复氧损伤中的作用[J]. 中国应用生理学杂志, 2006, 22(2): 136-140.
[8]	Nian M, Lee P, Khaper N, et al. Inflammatory cytokines and postmyocardial infarction remodeling [J]. Circ Res, 2004, 94(12): 1543-1553.
[9]	de Oliveira SG, Claudio ERG, de Almeida SA, et al. Exercise training improves vascular reactivity in ovariectomized rats subjected to myocardial infarction [J]. PLoS One, 2019, 14(4): e0215568.
[10]	Zhao D, Sun Y, Tan Y, et al. Short-duration swimming exercise after myocardial infarction attenuates cardiac dysfunction and regulates mitochondrial quality control in aged mice [J]. Oxid Med Cell Longev, 2018, 2018: 4079041.
[11]	Kuroda J, Ago T, Matsushima S, et al. NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart [J]. Proc Natl Acad Sci U S A, 2010, 107(35): 15565-15570.
[12]	Yu L, Yang G, Zhang X, et al. Megakaryocytic leukemia 1 bridges epigenetic activation of NADPH oxidase in macrophages to cardiac ischemia-reperfusion injury [J]. Circulation, 2018, 138(24): 2820-2836.
[13]	Pires Da Silva J, Monceaux K, Guilbert A, et al. SIRT1 protects the heart from ER stress-induced injury by promoting eEF2K/eEF2-dependent autophagy [J]. Cells, 2020, 9(2): 426.
[14]	Li D, Wang X, Huang Q, et al. Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-kappaB pathway in vivo and in vitro [J]. Redox Biol, 2018, 15: 62-73.
[15]	Yang H, Wang C, Zhang L, et al. Rutin alleviates hypoxia/reoxygenation-induced injury in myocardial cells by up-regulating SIRT1 expression [J]. Chem Biol Interact, 2019, 297: 44-49.
[16]	Donniacuo M, Urbanek K, Nebbioso A, et al. Cardioprotective effect of a moderate and prolonged exercise training involves sirtuin pathway [J]. Life Sci, 2019, 222: 140-147.
[17]	Dioum EM, Chen R, Alexander MS, et al. Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1 [J]. Science, 2009, 324(5932): 1289-1293.
[18]	Yang G, Weng X, Zhao Y, et al. The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction [J]. Nat Commun, 2017, 8: 14941.
[19]	Chen A, Chen Z, Xia Y, et al. Liraglutide attenuates NLRP3 inflammasome-dependent pyroptosis via regulating SIRT1/NOX4/ROS pathway in H9c2 cells [J]. Biochem Biophys Res Commun, 2018, 499(2): 267-272.
[20]	Gano LB, Donato AJ, Pasha HM, et al. The SIRT1 activator SRT1720 reverses vascular endothelial dysfunction, excessive superoxide production, and inflammation with aging in mice [J]. Am J Physiol Heart Circ Physiol, 2014, 307(12): H1754-1763.