تاثیر انواع فعالیت ورزشی بر بیان ژن‌های مرتبط با هدایت قلبی در رت‌های سالمند

نوع مقاله : مقاله پژوهشی

نویسندگان

1 دانشجوی دکتری فیزیولوژی ورزشی، دانشکده علوم ورزشی و تندرستی، دانشگاه شهید بهشتی، تهران، ایران.

2 استاد گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی و تندرستی، دانشگاه شهید بهشتی، تهران، ایران.

3 استادیار گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی و تندرستی، دانشگاه شهید بهشتی، تهران، ایران.

4 استاد گروه گردش خون و تصویربرداری پزشکی، دانشکده پزشکی و علوم بهداشت، دانشگاه علم و صنعت نروژ (NTNU)، تروندهایم، نروژ

چکیده

زمینه و هدف: در دوران سالمندی مشکلات هدایت قلبی و آریتمی، یکی از علل اصلی مرگ و میر در این افراد است. هدف از مطالعه حاضر بررسی تاثیر انواع فعالیت ورزشی بر بیان ژن‌‌های مرتبط با هدایت قلبی در رت‌های سالمند بود. روش تحقیق: آزمودنی‌های این مطالعه 24 سر رت نر ویستار 23 ماهه با وزن 45±465 گرم بودند که پس از تعیین حداکثر بار فعالیت، به‌طور تصادفی در چهار گروه مساوی (هر گروه شش سر) شامل کنترل، فعالیت شنای تداومی با شدت متوسط (MICE)، فعالیت شنای تناوبی با شدت و حجم بالا (HIIE-HV) و فعالیت شنای تناوبی با شدت بالا و حجم کم (HIIE-LV) قرار گرفتند. بعد از اتمام فعالیت، رت‌ها سریعا بیهوش و تشریح شدند. بافت گره های SA و AV قلبی برای بیان ژن‌های عامل 4رونویسی GATA (GATA4)، پروتئین کیناز B (AKT)، عامل پیش برنده میوسیت C2 (MEF2C) و عامل 5 رونویسی T-box (Tbx5) مورد استفاده قرار گرفت. به منظور بررسی بیان ژن های مذکور از روش آزمایشگاهی Real-time PCR  استفاده شد. برای بررسی نتایج از آزمون تحلیل واریانس یک راهه و آزمون تعقیبی توکی در سطح 05/0>p استفاده شد. یافته‌ها: تحلیل داده‌ها نشان داد HIIE-HV درگره SA و AV باعث افزایش معنی دار بیان ژن های AKT1 (به ترتیب با 0/001=p و 0/001=p)، GATA4 (به ترتیب با 0/001=p و 0/001=p)، MEF2C (به ترتیب با 0/01=p و 0/001=p) و Tbx5 (به ترتیب با 0/001=p و 0/001=p) شد. HIIE-LV فقط در گره SA باعث افزایش معنی بیان ژن‌های AKT1 (0/01=p)، GATA4 (0/005=p ) و Tbx5 (0/009=p) شد؛ در حالیکه بیان ژن های AKT1 (0/43 =p)، GATA4 (0/21=p)، Tbx5 (0/19=p) و MEF2C (0/44=p) در گره AV تغییر معنی داری نداشت. هم چنین در پاسخ به MICE، در گره SA و AV بیان ژن های AKT1 (به ترتیب با 0/29=p و 0/11=p)، GATA4 (به ترتیب با 0/15 =p و 0/72=p)، MEF2C (به ترتیب با 0/31=p و 0/85=p) و Tbx5 (به ترتیب با 0/98=p و 0/84=p) تغییر معنی داری نداشت. نتیجه گیری: تحقیق حاضر نشان داد HIIE-HV و HIIE-LV نسبت MICE می تواند باعث افزایش معنی دار بیان ژن های مرتبط با هدایت قلبی در رت‌های سالمند شود و این تغییرات می تواند باعث ارتقاء عملکرد سیستم هدایت الکتریکی قلب، بهبود آریتمی و کاهش مرگ و میر در افراد سالمند شود.  

کلیدواژه‌ها

عنوان مقاله [English]

The effect of different acute exercises on the expression of genes responsible for cardiac conduction in elderly rats

نویسندگان [English]

  • Zahra Amraei 1
  • Sajad Ahmadizad 2
  • Rana Fayazmilani 3
  • Ulrik Wisloff 4
1 PhD Student in Exercise Physiology, Faculty of Sport and Health Sciences, Shahid Beheshti University, Tehran, Iran.
2 Professor at Faculty of Sport and Health Sciences, Shahid Beheshti University, Tehran, Iran.
3 Assistant Professor at Faculty of Sport and Health Sciences, Shahid Beheshti University, Tehran, Iran.
4 Professor at Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
چکیده [English]

Extended Abstract
Background and Aim: Aging is a significant risk factor for the development of cardiac conduction disorders like arrhythmia. It impairs  cardiac conduction by disrupting the electrical conduction channels in the heart. Among the most evident physiological changes associated with aging are the morphological alterations in the cardiovascular system. Unfortunately, these changes diminish the overall function of the cardiovascular system, particularly affecting the cardiac conduction system in elderly individuals.
 Numerous studies have shown that the function of these channels and connexins is regulated by various genes, including GATA transcription factor 4 (GATA4), protein kinase B (AKT), myocytes enhancer factor type 2C (MEF2C), and T-box transcription factor 5 (Tbx5). Additionally, research suggests that physical activity and exercise can mitigate the progression of cardiac conduction disorders in aging individuals.. The aim of this study was to investigate the effect of different acute exercises on the expression of genes responsible for cardiac conduction in elderly rats. 
Materials and Methods: Twenty-four old male Wister rats (23 months, weigh 465±45 g) were recruited and divided into four groups (each group consist of six elderly rats), include of control, moderate intensity continuous exercise (MICE), high intensity interval exercise-low volume (HIIE-LV), and high intensity interval exercise-high volume (HIIE-HV) groups. Rats were maintained under controlled conditions with 75–85% humidity, 23±2°C temperature, and a 12-h light–dark cycle. 
Prior to the commencement of the study, ethical approval was obtained from the Ethics Committee for Biological Research at Shahid Beheshti University. All rats underwent a familiarization protocol to acclimate them to the pool and the exercise regimen. This protocol involved placing the rats in shallow water at 32°C for three consecutive days, with each session lasting 10 minutes.
Following the familiarization phase, the maximum exercise load for each rat was individually determined to establish exercise intensity and workload. To assess the maximum exercise load, a metal weight equivalent to 5% of the rat’s body weight was attached to the end of their tails using leucoplast tape. After a warm-up period, the workload was increased by 1 g every five minutes of swimming until the rats reached exhaustion. The maximum exercise load was defined as the highest load the rats could carry until exhaustion.
The MICE protocol consisted of 35 min swimming at 65% of maximal workload. The HIIE-HV consisted of 35 min interval swimming encompassed five sets of four min swimming at 85% of maximal workload and three min of passive recovery. The HIIE-LV consisted of seven min interval swimming encompassed 14 sets of 30 s swimming at 110 % of maximal workload interspersed by 30 s of passive recovery. After exercise sessions, all rats were anesthetized and sacrificed. SA and AV node tissue was used to examine the expression of GATA4, AKT, MEF2C, and Tbx5. Real-Time Quantitative PCR was used to analyses gene expression. For data analysis, One-way ANOVA and Tukey post hoc tests were utilized at p<0.05 level.
Results: Analysis of the data revealed that the expression of AKT1 (p=0.001 in the SA node and p=0.001 in the AV node), GATA4 (p=0.001 in both nodes), MEF2C (p=0.01 in the SA node and p=0.001 in the AV node), and Tbx5 (p=0.001 in both nodes) genes increased significantly after HIIE-HV compared to the control group.
In the SA node, the expression of AKT1 (p=0.01), GATA4 (p=0.005), and Tbx5 (p=0.009) genes also increased significantly after HIIE-LV compared to the control group. However, the expression of AKT1 (p=0.43), GATA4 (p=0.21), Tbx5 (p=0.19), and MEF2C (p=0.44) genes in the AV node did not change significantly.
In response to MICE, the expression of AKT1 (p=0.29 in the SA node and p=0.11 in the AV node), GATA4 (p=0.15 in the SA node and p=0.72 in the AV node), MEF2C (p=0.31 in the SA node and p=0.85 in the AV node), and Tbx5 (p=0.98 in the SA node and p=0.84 in the AV node) did not change significantly in either the SA or AV nodes (Table 1).
Conclusion: The HIIE-LV and HIIE-HV significantly increase the expression of genes related to cardiac conduction in elderly rats compared to MICE. This increase may enhance the function of the cardiac electrical conduction system, improve arrhythmias, and reduce mortality in elderly individuals by activating various molecular and cellular signaling pathways. Despite the limited information available on the signals associated with cardiac conduction and exercise, it appears that calcium-related mechanisms (such as calcium calmodulin and protein kinase C), mechanisms related to the tension-stretch of the atrial and ventricular walls during diastolic filling (increased preload and activation of focal adhesion kinase, FAK), and mechanisms related to cellular metabolism (protein kinase A and cyclic AMP, cAMP) are likely candidates for mediating the expression of cardiac conduction genes in response to exercise. Additionally, this study found that the expression of genes related to cardiac conduction in the SA node increased significantly even with intense exercise of short duration (seven minutes). In contrast, in the AV node, the expression of these genes increased significantly only with prolonged intense exercise. Although a specific mechanism explaining the differential expression of these genes in the SA and AV nodes has not yet been proposed, it is suggested that the varying degrees of stimulation from the autonomic nervous system (including parasympathetic inhibition and sympathetic activation) may contribute to these differences.
Ethical Considerations: This study was conducted based on the ethical guidelines for animal studies. The study protocol was approved by the Ethics Committee of Shahid Beheshti University Ethics Code: IR.SBU.REC.1403.134.
Compliance with Ethical Guidelines: Throughout all stages of the present study, all ethical principles for working with laboratory animals were observed following the NIH, IASP, and ARRIVE guidelines for the care and use of laboratory animals.
Funding: This study received no funding from public, commercial, or nonprofit organizations.
Conflicts of Interest: The authors declare no conflict of interest.

کلیدواژه‌ها [English]

  • Continuous swimming
  • Interval swimming
  • Aging
  • Cardiac conduction
  • Cardiac gene expression. 

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مطالعات کاربردی علوم زیستی در ورزش
دوره 13، شماره 36
دی 1404
صفحه 88-101

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