Razi Journal of Medical Sciences

fa تاثیر یک دوره بی‌تمرینی به دنبال تمرینات هوازی تداومی و تمرینات تناوبی شدت بالا بر بیان ژن پروتئین کیناز فعال شده با آدنوزین مونوفسفات قلبی در رت‌های دیابتی شده با آلوکسان The Effect of A Detraining Period Following Continuous Aerobic Training and High-Intensity Interval Training on Cardiac Denosine Monophosphate-Activated Protein Kinase Gene Expression in Alloxan-Treated Diabetic Rats فیزیولوژی ورزش Exercise Physiology پژوهشي Research <div style="text-align: justify;">زمینه و هدف: پروتئین کیناز فعال شده با آدنوزین مونوفسفات (AMPK) یک حسگر انرژی با بیان ناهنجار در بیماری های مختلف از جمله دیابت است. با این حال، مطالعات کمی برگشت‌پذیری مزایای ناشی از ورزش را نشان داده‌اند. هدف از انجام تحقیق حاضر تعیین تاثیر یک دوره بی تمرینی به دنبال تمرینات هوازی و AMPK قلبی در رتهای دیابتی بود. روش کار: برای انجام این تحقیق 48 سر رت نر ویستار 10 هفته‌ای با وزن 20±220 گرم به‌طور تصادفی در شش گروه 8 تایی تقسیم شدند. یک گروه به عنوان کنترل سالم در نظر گرفته شد و بقیه رت ها با استفاده از تک دوز 90 میلی گرم الوکسان به ازای وزن بدن دیابتی شدند. یک گروه به عنوان دیابت کنترل در نظر گرفته شد. و بقه رت ها در دو گروه تمرینات هوازی تداومی و تناوبی شدت باالا تقسیم شدند. پس از 12 هفته تمرینات نصف رت های هر گروه قربانی شدند. و بقه رت ها نیز 2 هفته پس از بی تمرینی قربانی شدند.  برنامه تمرین هوازی تداومی برای 5 جلسه در هفته با افزایش تدریجی سرعت‌ (18 الی 26 متر بر دقیقه) و زمان (10 الی 55 دقیقه) انجام گرفت. برنامه تمرین تناوبی شدت بالا نیز شامل 5 جلسه 30 دقیقهای در هفته در قالب دویدن روی تردمیل با تکرارهای یک‌دقیقه‌ای و استراحت فعال 2 دقیقه‌ای بین هر تناوب بود. به منظور تجزیه و تحلیل آماری از آزمون تحلیل واریانس یک طرفه و آزمون تعقیبی توکی استفاده شد و سطح معنی داری (05/0 ≥ P) در نظر گرفته شد. یافته‌ها: نتایج نشان داد القای دیابت موجب کاهش بیان ژن AMPK قلبی نسبت به گروه کنترل سالم شد (001/0 > P)، همچنین نتایج نشان داد که پس از 12 هفته تمرین افزایش معنی داری در بیان ژن AMPK قلبی در گروه های تمرین نسبت به گروه کنترل دیابت مشاهده شد (001/0 > P) ولی تفاوت معنی داری بین دو گروه تمرین مشاهده نشد (05/0 < P). همچنین نتایج نشان داد که پس از 2 هفته بی تمرینی کاهش جزئی در بیان ژن AMPK قلبی نسبت به گروه های تمرین مشاهده شد و لی این تغییرات معنی دار نبود (05/0 < P). نتیجه گیری: با توجه به نتایج می‌توان گفت که تمرینات ورزش با بیان ژن AMPK موجب حفاظت قلبی در برابر کاردیومیوپاتی دیابتی می‌شود و این اثر 2 هفته پس از بی تمرینی نیز همچنان باقی می‌ماند. </div> <div style="text-align: justify;">Background & Aims: Diabetes mellitus is one of the most common chronic diseases in the world (1). Diabetes and hyperglycemia caused by diabetes lead to disorders in various organs such as lungs, heart, muscles, kidneys, etc. (9, 10). One of the main complications of diabetes is diabetic cardiomyopathy; Diabetic cardiomyopathy is the result of diabetes-induced changes in the structure and function of the heart. Diabetic cardiomyopathy occurs as a result of impaired glucose and lipid metabolism associated with diabetes, which leads to increased oxidative stress and activation of multiple inflammatory pathways that mediate cellular and extracellular damage, pathological remodeling of the heart, and diastolic and systolic dysfunction. Preclinical studies in animal models of diabetes have identified several intracellular pathways involved in the pathogenesis of diabetic cardiomyopathy and potential cardioprotective strategies for disease prevention and treatment, including anti-fibrotic agents, anti-inflammatory agents, and antioxidants (11). Cellular energy homeostasis is a fundamental process that governs the overall health of the cell and is critical for cell survival. Central to this is the control of ATP production and utilization, which is regulated by a myriad of enzymatic reactions controlling cellular metabolism (12). Adenosine monophosphate-activated protein kinase (AMPK) is an energy sensor with aberrant expression in various diseases, including diabetes (12). There is considerable evidence that AMPK is reduced in cardiac tissues of animals and humans with type 2 diabetes or metabolic syndrome compared with non-diabetic controls, and that AMPK stimulation (physiological or pharmacological) can ameliorate diabetes-related cardiovascular complications (14). Considering the role of AMPK in energy metabolism in the heart, as well as the effects of diabetes and exercise on the gene and protein expression of this energy sensor, measuring the changes of this gene can improve our knowledge about the effect of different adaptations caused by different exercises, as well as the effect of lack of exercise. With the aim of investigating the effect of maintaining these adaptations after training (22, 23). However, so far, no research has been done that specifically compares the effect of two common training methods, continuous and intermittent training, followed by no training on cardiac AMPK gene expression in diabetic rats, which shows the necessity of the current research. According to the mentioned information, the present study was conducted with the aim of comparing the effect of a detraining period followed by aerobic and HIIT exercises on cardiac AMPK gene expression in alloxan-treated diabetic rats. Methods: In this experimental research, 48 male Wistar rats (age: 10-weeks; weigh: 220±20 grams) were randomly divided into six groups (n=8). One group was considered as a healthy control and the rest of the rats were made diabetic using a single dose of 90 mg/kg of alloxan. One group was considered as diabetic control; and the rats were divided into two groups of high-intensity interval training (HIIT) and continuous moderate aerobic training (MICT). After 12 weeks of training, half of the rats in each group were sacrificed; and the rats were sacrificed after 2 weeks of no training. MICT program was performed for 5 sessions per week with a gradual increase in speed (18-26 m/min) and time (10-55 minutes). HIIT program also included 5 30-minute sessions per week in the form of running on a treadmill with one-minute repetitions and 2-minute active rest between each interval. For statistical analysis, one-way analysis of variance and Tukey's post hoc test were used and the significance level (P ≤ 0.05) was considered. Results: The results showed that the induction of diabetes decreased the cardiac AMPK gene expression compared to the healthy control group (P < 0.001), also the results showed that after 12 weeks of training, there was a significant increase in the cardiac AMPK gene expression in the training groups compared to the control group. Diabetes control was observed (P < 0.001), but no significant difference was observed between the two exercise groups (P > 0.05). Also, the results showed that after 2 weeks of non-training, there was a slight decrease in cardiac AMPK gene expression compared to the training groups, and these changes were not significant (P > 0.05). Conclution: The results of the present study showed that induction of diabetes with alloxan decreased cardiac AMPK gene expression, which was related to hyperglycemia caused by induction of diabetes with alloxan injection. Previous research has also shown that a single dose of alloxan injection with 90 mg/kg body weight of rats induces diabetes (24-26). According to the findings of the present study, 12 weeks of continuous aerobic exercise and HIIT both significantly increased cardiac AMPK gene expression in diabetic rats, but no significant difference was observed between the two types of exercise. Based on the research conducted in animal models, exercise increases cardiac AMPK values, which are consistent with the results of the present study (30, 31). However, comparing the effects of continuous and HIIT exercises, the results of these two studies were different from our findings; In their research comparing the effect of moderate intensity continuous training and HIIT training on AMPK of skeletal and cardiac muscle, Wen et al. reported that the effects of HIIT training on increasing oxidative capacity and AMPK are more obvious (30); The results of Su et al.'s research showed better effects of continuous training on AMPK and PGC-1α gene expression in the HIIT group than continuous aerobic training (30). As shown in various animal models and patient studies, physical exercise is known to be cardioprotective and can partially compensate for cardiac damage. At the cellular level, exercise counteracts heart disease-related changes in these cellular pathways and can improve heart function (32). AMPK activation leads to the regulation of metabolism, protein transport, transcription factors and/or activators, kinases, and other enzymes and non-enzymatic proteins. AMPK increases substrate uptake and utilization in the heart, enhances mitochondrial biogenesis, and modulates the activity of specific proteins and transcription factors to exert cardioprotective functions (33). Therefore, exercise training can moderate the effects of diabetes on the heart by increasing cardiac AMPK. AMPK also plays an important role in reducing oxidative stress, regulating autophagy and anti-apoptosis of cardiomyocytes (29, 34). Exercise activates signaling molecules and transcriptional networks to promote physiological adaptations such as mitochondrial biogenesis (35). It has been reported that after swimming exercises in rats, the levels of activated AMPK showed a decrease in cardiac fibrosis due to the inhibition of NADPH oxidase (36). This finding has been confirmed as decreased AMPK activity by beta-adrenergic activation exacerbates cardiac fibrosis (37). These changes are important because exercise activates AMPK and thus may be able to inhibit pathological hypertrophy and cardiac fibrosis (38). Other findings of our research showed that 2 weeks of detraining after exercise decreased AMPK in both exercise groups, but this decrease was not statistically significant. In line with the findings of the current research, Cao et al also reported in their research that after the training period, a significant increase in AMPK level was observed, but after stopping training for 10 days, the AMPK level started to decrease, but the changes were not significant 40). Based on the results, it can be said that any two methods of continuous aerobic exercise and HIIT increase the expression of the AMPK gene; Also, after two weeks ofdetraining, cardiac AMPK gene expression is still high in diabetic rats. However, more research is needed to investigate the longer-term effects of non-exercise on AMPK gene expression and mechanisms related to non-exercise on diabetic cardiomyopathy.</div> دیابت, قلب, تمرین تناوبی شدت بالا, بی‌تمرینی, پروتئین کیناز فعال شده با آدنوزین مونوفسفات Diabetes, Heart, High intensity interval training, Detraining, Protein kinase activated by adenosine monophosphate 510 519 http://rjms.iums.ac.ir/browse.php?a_code=A-10-7194-2&slc_lang=fa&sid=1 Masoumeh Dolatabadi معصومه دولت آبادی 3900319475328460075599 3900319475328460075599 No PhD Student, Department of Cardiovascular and Respiratory Sports Physiotherapy, Central Tehran Branch, Islamic Azad University, Tehran, Iran دانشجوی دکتری، گروه فیریولوزی ورزشی قلب وعروق تنفس، واحد تهران مرکزی، دانشگاه آزاد اسلامی‌، تهران، ایران Hasan Matinhomaee حسن متین همایی hasanmatinhomaee@gmail.com 3900319475328460075600 3900319475328460075600 Yes Associate Professor, Department of Cardiovascular and Respiratory Sports Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran دانشیار، گروه فیزیولوژی ورزشی قلب و عروق و تنفس، واحد تهران مرکزی، دانشگاه آزاد اسلامی، تهران، ایران Farshad Ghazalian فرشاد ‌غزالیان 3900319475328460075601 3900319475328460075601 No Associate Professor, Department of Physical Education, Sports Sciences, Science and Research Unit, Islamic Azad University, Tehran, Iran دانشیار، گروه تربیت بدنی، علوم ورزشی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران