نوع مقاله : مقاله پژوهشی
نویسندگان
1 دانشجوی دکتری فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه شهید چمران اهواز، اهواز، ایران.
2 استاد گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه شهید چمران اهواز، اهواز، ایران.
3 استادیار گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی ، دانشگاه شهید چمران اهواز، اهواز، ایران.
چکیده
کلیدواژهها
عنوان مقاله [English]
نویسندگان [English]
Extended Abstract
Background and Aim: Glucocorticoids are among the most commonly prescribed classes of drugs worldwide, so that the using of these drugs has steadily increased in recent years. Dexamethasone-induced hypertension is a well-recognized side effect that occurs following chronic administration in both animals and humans. Hypertension leads to cardiac remodeling characterized by pathological hypertrophy, reduced capillary density, and increased fibrosis. Cardiac fibrosis is a pathological extracellular matrix (ECM) remodeling process that results in abnormalities in the composition and quality of the matrix, as well as impaired myocardial function. However, excessive and persistent ECM deposition, particularly increased type I collagen secretion, could leads to tissue dysfunction. These drugs can affect cardiac tissue remodeling by disrupting the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases, resulting in ECM remodeling, cellular hypertrophy, collagen fiber accumulation, and ultimately restriction of normal organ function. Moreover, transforming growth factor-β1 (TGF-β1) is well established as one of the principal cytokines involved in the initiation and progression of the fibrotic process. Although antihypertensive treatments may lead to adverse effects and alter the clinical course of the disease, identifying safe and natural alternative therapies remains a primary objective.
Exercise training, due to its compensatory and regulatory effects on biological systems, is widely used for the prevention and treatment of various diseases. Most researchers believe that regular physical activity may exert a negative regulatory or inhibitory effect on the TGF-β1 signaling cascade by influencing its activating factors. Consequently, regular exercise training is considered an effective non-pharmacological intervention for the control of hypertension and can attenuate pathological cardiac remodeling while improving arterial stiffness. Therefore, the present study aimed to investigate the effects of six weeks of resistance and continuous aerobic training on type I collagen content and ECM proteins in the myocardial tissue of female rats with Dexamethasone (DEX)-induced hypertension
Materials and Methods: This experimental–laboratory study was conducted on 12 adult female Wistar rats with a mean age of four weeks and an average body weight of 200–250 g. The animals were housed under standard laboratory conditions with controlled temperature, humidity, and light–dark cycles, and had ad libitum access to food and water. The rats were randomly assigned into four equal groups including healthy control, DEX-induced control, DEX plus resistance training, and DEX plus continuous aerobic training. Hypertension was induced by subcutaneous injection of DEX at a dose of 0.1 mg per 100 g of body weight for 10 consecutive days. The resistance training protocol consisted of ladder climbing on an 80° incline with a length of 110 cm, during which a load equivalent to 60% of the animal’s body weight was attached to the tail, that follow with three sessions per week for six weeks. In contrast, the continuous aerobic training protocol involved treadmill running at moderate intensity, progressively increasing from 60% to 70% of the animals’ maximal running speed over the same training period. At the end of the training intervention, the animals were anesthetized using appropriate anesthetic agents and subsequently sacrificed. In this way, the left ventricle was excised from the heart tissue for analysis. Following tissue extraction, the protein levels of type I collagen, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), and TGF-β1 were quantified using Western blotting and enzyme-linked immunosorbent assay (ELISA) techniques. For statistical analysis, the Shapiro–Wilk test was applied to assess data normality, and Levene’s test was used to evaluate the homogeneity of variances. In addition, one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test was employed to determine significant differences among groups. The level of statistical significance was set at p<0.05.
Findings: The DEX induced lead to significant reduction in body weight (p=0.001) and a decrease in MMP-2 protein levels (p=0.001), whereas the protein levels of type I collagen (p=0.001), TIMP-1 (p=0.001), and TGF-β1 (p=0.001) were significantly increased. Moreover, MMP-2 protein levels increased in both exercise-trained groups compared with the Dex-induced control group (p=0.001); however, continuous aerobic training showed a significantly greater increase in this marker (p=0.03). Moreover, TIMP-1 levels decreased in both exercise-trained groups compared to Dex-induced control group (p=0.001); while in the aerobic continuous training and resistance training groups indicated significantly reduction as compare to control group (p=0.02). On the other hand, type I collagen was reduced in both exercise groups (p=0.001), with no significant difference between the training modalities (p=0.95). In addition, TGF-β1 levels decreased in both exercise groups compared to Dex-induced control group (p=0.001); however, no significant difference was observed between the two exercise interventions (p=0.43).
Conclusion. It is believed that exercise could inhibit TGF-β/Smad3 signaling pathway by up-regulating the expression of cardiac endotelial proginator cells-derived exosomal miR-126, thereby weakening the trans differentiation of cardiac fibroblasts into myofibroblasts and reduce the production of collagen fibers. Also, the mechanism of the action of MMP- 2 was different according to the type of training and its adaptation in muscle and cardiomyocytes. In this way, two possibilities can be considered in regarding to the aerobic training, first that the response of MMPs is transitory, because the peak of changes occurred during or during the first few hours after training, and secondly, the induction mechanism may be related to exercise (strength training) and intensity of exercises that indicates the effect of different types of exercise (with diverse methods) on mechanisms of angiogenesis and regeneration of ECM factors in different tissues. Researchers believe that regular exercise can create negative or blocking regulation in the TGF-β signaling cascade by affecting its activating factors. Reducing the expression of TGF-β and inhibiting its signaling pathway also can reduce the expression of genes involved in the production of ECM collagen. Moreover, performing long-term resistance training could increases the antioxidant capacity of the muscle. The occurrence of this training adaptation can lead to a decrease in the expression of this factor after a period of training. Since the molecular and genetic adaptation mechanisms induced by resistance and aerobic training are different, therefore based on the each type of exercise, a set of cellular signaling pathways and specific genes are activated. Therefore, regular exercise training is an effective non-pharmacological treatment for controlling high blood pressure and can reduce pathological cardiac remodeling and improve arterial stiffness. The results of this study also emphasize the importance of targeted exercise training as a safe, low-cost, non-pharmacological alternative for the prevention, control, and management of blood pressure.
Ethical Considerations: All ethical principles in this research were meticulously adhered to by the researchers and approved by the ethics commitee of the Shahid Chamran university of Ahvaz (IR.SCU.REC.1402.037).
Funding: The authors of this article declare that they have not received any financial support from any organization.
Conflicts of interest: The authors report no conflicts of interest in relation to this manuscript.
کلیدواژهها [English]
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