نوع مقاله : مقاله پژوهشی
عنوان مقاله English
نویسندگان English
Introduction and Purpose: Spinal Cord Injury (SCI) induces muscle atrophy by altering apoptosis-autophagy pathways. Pharmacological and exercise interventions can mitigate SCI complications. Therefore, this study aimed to investigate the effects of aerobic exercise, resveratrol supplementation, and their combination on the levels of BAX, BCL2, and BCL2/BAX apoptosis pathway proteins in gastrocnemius muscle.
Materials and Methods: Male Wistar rats, aged forty weeks, were categorized into five groups: healthy control, SCI control, SCI supplementation, SCI training, and resveratrol + training SCI. A spinal cord injury was inflicted by releasing a 10-gram weight from a height of 25 mm onto the spinal cord at the T10 segment. The resveratrol supplement was administered intraperitoneally on a daily basis at a dosage of 10 mg/kg. Aerobic exercise was conducted using a weight-support system for 4 weeks, lasting 58 minutes per session, at an intensity of 20 meters per minute. The levels of BAX and BCL2 in the gastrocnemius muscle were quantified using ELISA. The outcomes were examined utilizing an independent- t-test and one-way ANOVA with Tukey's post hoc analysis.
Results: The findings indicated that SCI resulted in a dramatic reduction in BCL2 protein levels and a diminished BCL2/BAX ratio in the gastrocnemius muscle of rats post-SCI, while BAX levels in the gastrocnemius muscle were significantly elevated. Eight weeks of training, combined with resveratrol administration and aerobic exercise, led to a notable elevation in BCL2 protein levels and the BCL2/BAX ratio in the gastrocnemius muscle relative to the SCI control group. Resveratrol administration, both with and without exercise, elevated BCL2 levels and the BCL2/BAX ratio in the gastrocnemius muscle relative to exercise alone. BAX protein levels diminished following all treatments. The findings indicated that the conjunction of exercise and resveratrol administration markedly elevated BCL2 levels and the BCL2/BAX ratio in the gastrocnemius muscle, in contrast to exercise or supplementation alone. In comparison to exercise alone, both supplementation with and without exercise markedly reduced BAX levels.
Discussion and Conclusion: Aerobic exercise, in conjunction with resveratrol administration, appears to suppress apoptosis via influencing the levels of BCL2, BAX, and the muscle BCL2/BAX ratio in rats with spinal cord injury.
Forty rats were divided into one healthy group and four SCI groups. The SCI groups were subjected to the following interventions: control, aerobic exercise, resveratrol supplementation, and combined aerobic exercise with resveratrol supplementation. Interventions commenced 14 days post-injury induction and lasted for eight weeks. Aerobic exercise training was performed for 58 minutes at a speed of 20 m/min. The rats were supplemented by a 10 mg dose administered via intraperitoneal injection.
The results showed that SCI significantly decreased BCL2 protein levels and the BCL2/BAX ratio, while significantly increasing BAX levels. Furthermore, eight weeks of aerobic exercise and the combined intervention (exercise + resveratrol) significantly increased BCL2 levels and the BCL2/BAX ratio. Resveratrol supplementation, both with and without exercise, elevated BCL2 levels and the BCL2/BAX ratio more significantly than exercise alone. However, BAX protein levels decreased in response to all interventions. The results also indicated that the combined exercise and resveratrol intervention significantly increased BCL2 and the BCL2/BAX ratio compared to either exercise or supplementation alone. Additionally,
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These findings suggest that aerobic exercise, resveratrol supplementation, and their combination can inhibit apoptosis by modulating the levels of key proteins involved in this pathway in rats with spinal cord injury.
کلیدواژهها English
1. Introduction and Purpose
Spinal Cord Injury (SCI) is a progressive neurological condition characterized by immediate mechanical damage (primary injury), followed by a cascade of secondary pathological events including inflammation, oxidative stress, mitochondrial dysfunction, and programmed cell death (apoptosis). These secondary processes exacerbate tissue damage, leading to persistent motor and sensory deficits. Resveratrol (RSV), a natural polyphenol abundant in grapes, berries, and peanuts, has emerged as a potent neuroprotective agent with multifaceted biological activities. Experimental evidence suggests that RSV administration following SCI reduces oxidative stress and mitigates inflammation. Furthermore, post-SCI use of RSV decreases apoptosis by downregulating the expression of BAX and Caspase-3 while simultaneously upregulating BCL2 expression. On the other hand, aerobic exercise provides neuroprotection by improving blood flow, enhancing the expression of neurotrophic factors, and modulating immune responses. In animal models of SCI, aerobic training (such as treadmill running at 20 m/min) reduces pro-inflammatory cytokines and increases anti-inflammatory mediators in the spinal cord tissue. However, the specific impact of exercise on apoptotic regulators like BAX and BCL2 following SCI remains largely unknown. Given the complex pathophysiology of SCI the initial injury followed by secondary damage expansion a definitive treatment for spinal cord repair has yet to be identified. Since the secondary phase of SCI is associated with significant functional decline, apoptosis, and muscle/tissue atrophy, one of the most critical therapeutic goals for SCI is to slow disease progression, inhibit secondary injury, and improve patient function. Therefore, the aim of this study was to investigate the effect of aerobic training combined with Resveratrol supplementation on the levels of BAX, BCL2, and the BCL2/BAX ratio in the gastrocnemius muscle of rats following SCI.
2. Materials and Methods
Forty male Wistar rats, 8 weeks old, were divided into 5 groups: Sham Control, SCI Control, SCI Supplementation (RSV), SCI Exercise, and SCI Resveratrol + Exercise. SCI was induced by dropping a 10 g weight from a height of 25 mm onto the spinal cord at the T10 segment. Resveratrol supplementation was administered daily via intraperitoneal (IP) injection at a dose of 10 mg/kg of body weight. Aerobic training, utilizing a weight-support system, was conducted for 4 weeks, with each session lasting 58 minutes at a speed of 20 m/min. Forty-eight hours after the final training session, rats were anesthetized using a combined IP injection. The right gastrocnemius muscle was then harvested from all rats. After excision and cleaning of blood, the muscle tissue was transferred to micro-tubes, snap-frozen using liquid nitrogen, and subsequently stored at 70 C. The protein levels of BAX and BCL2 in the gastrocnemius muscle were measured using the ELISA method. Data were analyzed using the Independent t-test and One-way Analysis of Variance (ANOVA) followed by the Tukey's post-hoc test.
3. Results
The results indicated that SCI was associated with a significant decrease in the protein level of BCL2 and the BCL2/BAX ratio in the rats’ gastrocnemius muscle post-SCI, while the BAX level in the gastrocnemius muscle showed a significant increase. Four weeks of exercise training and the combined intervention of Resveratrol supplementation with aerobic exercise resulted in a significant increase in gastrocnemius muscle BCL2 protein level and the BCL2/BAX ratio compared to the SCI Control group. Furthermore, Resveratrol supplementation, both with and without exercise, led to increased BCL2 levels and the BCL2/BAX ratio when compared to the Exercise-only group. BAX protein level decreased in response to all interventions. The results also demonstrated that the combination of exercise and Resveratrol supplementation significantly enhanced BCL2 and the BCL2/BAX ratio in the gastrocnemius muscle compared to exercise or supplementation alone. Moreover, compared to exercise alone, supplementation (with and without exercise) resulted in a significant decrease in BAX.
4. Conclusion
Previous research has shown that BAX and BCL2, which act as pro-apoptotic and anti-apoptotic factors, respectively, cooperatively form a heterodimer during acute SCI that determines the pathway of apoptosis progression. High levels of SCI-induced apoptosis can exacerbate neural damage. This study suggests that Resveratrol and aerobic exercise interactively modulate the BCL2/BAX axis to inhibit apoptosis in SCI rats. The superiority of Resveratrol over exercise in reducing BAX and increasing the BCL2/BAX ratio highlights its strong anti-apoptotic pharmacology, while their combination benefits from complementary mechanisms for enhanced efficacy. These findings support integrated pharmacological and rehabilitation approaches to mitigate secondary neuronal degeneration following spinal cord injury. Future studies should investigate translational protocols and long-term functional outcomes to leverage this synergy for the benefit of patients.
5. Acknowledgment & Funding
The authors would like to express their gratitude to all individuals who assisted in conducting this research and achieving its useful and practical results.
6. Ethical Consideration
All animal procedures in this study were conducted in accordance with the guidelines of the institutional and international standards for the care and use of laboratory animals. All efforts were made to minimize the number of animals used and to reduce suffering, including the use of appropriate anesthesia and humane endpoints.
7. Contribution of authors
All authors have contributed to the article. all authors read and approved the final manuscript.
8. Conflict of interest
The authors declare no conflict of interest.
