Volume 32, Issue 1 (3-2025)
RJMS 2025, 32(1): 1-18 |
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Research code: 0
Ethics code: IR.UMZ.REC.1401.020
Clinical trials code: 0
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Momeni M, Mirdar S, Ranaee M. Effects of Moderate-Intensity Interval Training Combined with Resistance Training on the Airway Remodeling in Male Wistar Rats Sensitized with Ovalbumin. RJMS 2025; 32 (1) :1-18
URL: http://rjms.iums.ac.ir/article-1-8220-en.html
URL: http://rjms.iums.ac.ir/article-1-8220-en.html
1- Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Iran
2- Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Iran, & Athletic Performance and Health Research Center, University of Mazandaran, Babolsar, Iran, & North Asa Hirbod Health and Sport Sciences Firm, University of Mazandaran, Babolsar, Iran ,shadmehr.mirdar@gmail.com
3- Department of Pathology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
2- Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Iran, & Athletic Performance and Health Research Center, University of Mazandaran, Babolsar, Iran, & North Asa Hirbod Health and Sport Sciences Firm, University of Mazandaran, Babolsar, Iran ,
3- Department of Pathology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
Abstract: (359 Views)
Background & Aims: Allergic asthma is characterized by persistent airway inflammation, mucus hypersecretion, epithelial barrier dysfunction, bronchial narrowing, and progressive airway remodeling. These changes are driven by interactions among inflammatory cells, structural airway cells, and mediators that damage the airway wall and impair respiratory function. Neutrophil elastase, released mainly from activated neutrophils, contributes to epithelial injury, mucus gland stimulation, extracellular matrix degradation, and amplification of allergic inflammation. Claudin-5, a tight junction–associated protein expressed in pulmonary epithelial and endothelial barriers, is involved in the regulation of airway permeability and structural integrity. Altered expression of these markers may therefore reflect inflammatory injury and remodeling in allergic asthma. Although regular exercise is increasingly recognized as a non-pharmacological strategy for improving respiratory health and physical capacity, the optimal training model for asthma remains uncertain. In particular, little is known about the effects of moderate-intensity interval training combined with resistance training on lung remodeling and related molecular markers. This study aimed to evaluate the effects of an eight-week program of moderate-intensity interval training, resistance training, and their combination on airway inflammation, airway remodeling, immunohistochemical expression of neutrophil elastase and claudin-5, serum IgE concentration, endurance capacity, and muscle strength in male Wistar rats sensitized with ovalbumin.
Methods: This experimental study was conducted on forty male Wistar rats, which were randomly divided into five groups: saline control, ovalbumin control, ovalbumin plus moderate-intensity interval training, ovalbumin plus resistance training, and ovalbumin plus combined training. Allergic asthma was induced by repeated intraperitoneal sensitization with ovalbumin and aluminum hydroxide during the first three weeks, followed by inhalational ovalbumin challenge three times per week for eight weeks. The interval training protocol was performed three times weekly for eight weeks and consisted of 30-minute sessions including repeated cycles of one minute of treadmill running and two minutes of active rest at 60–75% of maximal exercise capacity. Resistance training was performed three times weekly using a squat apparatus, with three sets of 10–12 repetitions at 60% of one-repetition maximum and 90 seconds of rest between sets. Rats in the combined training group performed the resistance protocol followed by the interval protocol. Forty-eight hours after the final session, blood and lung tissue samples were collected. Serum IgE was measured by ELISA. Lung histopathology was assessed using hematoxylin and eosin staining to evaluate inflammatory cell infiltration, mucus production, airway smooth muscle thickness, epithelial alterations, bronchial constriction, and morphological remodeling. Immunohistochemical and immunofluorescence staining were used to determine the expression of neutrophil elastase and claudin-5 in lung tissue. Endurance performance was evaluated using a maximal capacity treadmill test, and muscle strength was assessed by repeated one-repetition maximum testing. Data were analyzed using analysis of variance models, and statistical significance was accepted at P≤0.05.
Results: Ovalbumin sensitization successfully induced a pattern consistent with allergic asthma. Compared with the saline control group, ovalbumin-sensitized rats showed increased serum IgE, marked pulmonary inflammation, mucus hypersecretion, goblet cell changes, bronchial constriction, vascular changes, reduction of airway lumen, and increased airway smooth muscle thickness. These findings confirmed the development of airway inflammation and remodeling following allergen exposure. Immunohistochemical evaluation also showed stronger expression of neutrophil elastase and claudin-5 in the lung tissue of ovalbumin-sensitized animals, indicating activation of inflammatory and epithelial barrier–related responses. Exercise training did not significantly reduce serum IgE compared with the ovalbumin control group, suggesting that the main protective effects of training were not mediated by suppression of systemic IgE production. However, all exercise interventions attenuated several pulmonary abnormalities. Moderate-intensity interval training and resistance training reduced inflammatory infiltration and decreased the expression of neutrophil elastase and claudin-5 compared with the ovalbumin control group. The combined training protocol produced the most pronounced protective effects. In the combined training group, inflammatory cell infiltration, mucus production, airway smooth muscle thickening, epithelial damage, bronchial narrowing, and other structural remodeling features were markedly lower than in the ovalbumin control group. Quantitative evaluation showed that interval training reduced neutrophil elastase and claudin-5 expression, resistance training produced similar but slightly smaller reductions, and combined training resulted in the greatest decrease in both markers. Combined training reduced neutrophil elastase expression by approximately 20.34% and claudin-5 expression by approximately 23.69% compared with the interval training condition, suggesting an additive effect of integrating aerobic interval and resistance stimuli. Functional outcomes also improved after training. Resistance and combined training increased absolute and relative muscle strength over time, whereas interval and combined training improved speed, running time, distance, and overall endurance capacity. Among all ovalbumin-sensitized groups, the combined training group showed the most favorable profile, with simultaneous improvement in pulmonary structure, inflammatory marker expression, endurance performance, and muscle strength.
Conclusion: The findings indicate that eight weeks of moderate-intensity interval training combined with resistance training can attenuate allergen-induced airway inflammation and remodeling in a rat model of ovalbumin-induced allergic asthma. These beneficial effects appear to be associated with reduced lung expression of neutrophil elastase and claudin-5, decreased mucus production and airway smooth muscle thickening, and improved exercise capacity and skeletal muscle strength. Although exercise training did not significantly alter serum IgE, it improved local pulmonary and functional outcomes, suggesting that combined training may act mainly through modulation of airway inflammation, epithelial barrier-related responses, and peripheral conditioning rather than through systemic allergic sensitization. Overall, moderate-intensity combined exercise may represent a promising adjunctive non-pharmacological strategy for controlling airway remodeling and improving physical fitness in allergic asthma. Further studies are recommended to clarify the molecular mechanisms, optimal training intensity and duration, long-term safety, and translational relevance of this approach for patients with asthma.
Methods: This experimental study was conducted on forty male Wistar rats, which were randomly divided into five groups: saline control, ovalbumin control, ovalbumin plus moderate-intensity interval training, ovalbumin plus resistance training, and ovalbumin plus combined training. Allergic asthma was induced by repeated intraperitoneal sensitization with ovalbumin and aluminum hydroxide during the first three weeks, followed by inhalational ovalbumin challenge three times per week for eight weeks. The interval training protocol was performed three times weekly for eight weeks and consisted of 30-minute sessions including repeated cycles of one minute of treadmill running and two minutes of active rest at 60–75% of maximal exercise capacity. Resistance training was performed three times weekly using a squat apparatus, with three sets of 10–12 repetitions at 60% of one-repetition maximum and 90 seconds of rest between sets. Rats in the combined training group performed the resistance protocol followed by the interval protocol. Forty-eight hours after the final session, blood and lung tissue samples were collected. Serum IgE was measured by ELISA. Lung histopathology was assessed using hematoxylin and eosin staining to evaluate inflammatory cell infiltration, mucus production, airway smooth muscle thickness, epithelial alterations, bronchial constriction, and morphological remodeling. Immunohistochemical and immunofluorescence staining were used to determine the expression of neutrophil elastase and claudin-5 in lung tissue. Endurance performance was evaluated using a maximal capacity treadmill test, and muscle strength was assessed by repeated one-repetition maximum testing. Data were analyzed using analysis of variance models, and statistical significance was accepted at P≤0.05.
Results: Ovalbumin sensitization successfully induced a pattern consistent with allergic asthma. Compared with the saline control group, ovalbumin-sensitized rats showed increased serum IgE, marked pulmonary inflammation, mucus hypersecretion, goblet cell changes, bronchial constriction, vascular changes, reduction of airway lumen, and increased airway smooth muscle thickness. These findings confirmed the development of airway inflammation and remodeling following allergen exposure. Immunohistochemical evaluation also showed stronger expression of neutrophil elastase and claudin-5 in the lung tissue of ovalbumin-sensitized animals, indicating activation of inflammatory and epithelial barrier–related responses. Exercise training did not significantly reduce serum IgE compared with the ovalbumin control group, suggesting that the main protective effects of training were not mediated by suppression of systemic IgE production. However, all exercise interventions attenuated several pulmonary abnormalities. Moderate-intensity interval training and resistance training reduced inflammatory infiltration and decreased the expression of neutrophil elastase and claudin-5 compared with the ovalbumin control group. The combined training protocol produced the most pronounced protective effects. In the combined training group, inflammatory cell infiltration, mucus production, airway smooth muscle thickening, epithelial damage, bronchial narrowing, and other structural remodeling features were markedly lower than in the ovalbumin control group. Quantitative evaluation showed that interval training reduced neutrophil elastase and claudin-5 expression, resistance training produced similar but slightly smaller reductions, and combined training resulted in the greatest decrease in both markers. Combined training reduced neutrophil elastase expression by approximately 20.34% and claudin-5 expression by approximately 23.69% compared with the interval training condition, suggesting an additive effect of integrating aerobic interval and resistance stimuli. Functional outcomes also improved after training. Resistance and combined training increased absolute and relative muscle strength over time, whereas interval and combined training improved speed, running time, distance, and overall endurance capacity. Among all ovalbumin-sensitized groups, the combined training group showed the most favorable profile, with simultaneous improvement in pulmonary structure, inflammatory marker expression, endurance performance, and muscle strength.
Conclusion: The findings indicate that eight weeks of moderate-intensity interval training combined with resistance training can attenuate allergen-induced airway inflammation and remodeling in a rat model of ovalbumin-induced allergic asthma. These beneficial effects appear to be associated with reduced lung expression of neutrophil elastase and claudin-5, decreased mucus production and airway smooth muscle thickening, and improved exercise capacity and skeletal muscle strength. Although exercise training did not significantly alter serum IgE, it improved local pulmonary and functional outcomes, suggesting that combined training may act mainly through modulation of airway inflammation, epithelial barrier-related responses, and peripheral conditioning rather than through systemic allergic sensitization. Overall, moderate-intensity combined exercise may represent a promising adjunctive non-pharmacological strategy for controlling airway remodeling and improving physical fitness in allergic asthma. Further studies are recommended to clarify the molecular mechanisms, optimal training intensity and duration, long-term safety, and translational relevance of this approach for patients with asthma.
Type of Study: Research |
Subject:
Exercise Physiology
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