نوع مقاله : مقاله پژوهشی Released under CC BY-NC 4.0 license I Open Access I
نویسندگان
1 گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی وتندرستی، دانشگاه تهران، تهران، ایران
2 گروه تربیت بدنی و علوم ورزشی، واحد مرند، دانشگاه آزاد اسلامی، مرند، ایران
3 دانشکده تربیت بدنی و علوم ورزشی دانشگاه تهران، تهران، ایران
4 مرکز تحقیقات کاربردی دارویی دانشگاه علوم پزشکی تبریز، دانشیار، تبریز، ایران
چکیده
مقدمه: دوکسوروبیسین داروی مؤثری در درمان انواع سرطان است، ولی کاربرد آن به‌دلیل سمیت قلبی محدود شده است. دربارۀ تأثیر محافظتی تمرین تناوبی شدید در مقابل سمیت قلبی ناشی از دوکسوروبیسین و مکانیسم‌های آن تحقیقات نادری وجود دارد. هدف این تحقیق بررسی تأثیر تمرین تناوبی شدید پیش از القای دوکسوروبیسین بر میزان بیان miR-499، که به‌طور گسترده‌ای در شرایط فیزیولوژیکی در قلب بیان می‌شود، در سلول‌های قلبی است.
روش پژوهش: 24 سر رت نر ویستار به‌طور تصادفی به چهار گروه (6=n) تقسیم شدند: 1- کنترل-سالین (Control)؛ درمان با دوکسوروبیسین (20 میلی‌گرم/کیلوگرم وزن بدن) (DOX)؛ 2- تمرینات تناوبی شدید (HIIT) (هشت هفته، 7 ست 4 دقیقه‌ای 80-90 درصد VO2max مجزاشده با دوره‌های سه‌دقیقه‌ای 65–75 درصد VO2max) و درمان با دوکسوروبیسین پس از اتمام آخرین جلسة تمرینات تناوبی شدید (HIIT+DOX). بررسی میزان بیان miR-499 با روش RT-PCR انجام گرفت. از تجزیه‌وتحلیل واریانس یکطرفه و سپس آزمون تعقیبی توکی برای بررسی آماری داده‌ها استفاده شد (05/0>α).
یافته‌ها : نتایج نشان داد القای دوکسوروبیسین بیان miR-499 را به‌طور معنا‌داری در بافت بطن چپ قلب افزایش می‌دهد (05/0>P). همچنین میزان بیان miR-499 پس از تمرین افزایش یافت، ولی این تفاوت از نظر آماری معنا‌دار نبود. تمرین پیش از القای دوکسوروبیسین نیز موجب کاهش معنا‌دار میزان بیان miR-499 در گروهHIIT+DOX نسبت به گروه DOX شد (05/0>P). بنابراین انجام تمرین تناوبی شدید پیش از القای دوکسوروبیسین می‌تواند تغییرات بیان miR-499 ناشی از دوکسوروبیسین را کاهش دهد.
نتیجه‌گیری: نتیجه اینکه تمرین تناوبی شدید می‌تواند روش مناسبی در محافظت قلب در برابر سمیت قلبی ناشی از دوکسوروبیسین از طریق کاهش میزان بیان miR-499 باشد.
کلیدواژه‌ها
موضوعات
عنوان مقاله [English]
Protective Effect of High-Intensity Interval Training on Doxorubicin-Induced Cardiotoxicity by Reducing MiR-499 Expression in Male Rats
نویسندگان [English]
- Siroos Choobineh 1
- Khadijeh Ebrahimi 2
- Rahman Soori 3
- Reza Badalzadeh 4
1 Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran.
2 Corresponding Author, Department of Physical Education and Sport Sciences, Marand Branch, Islamic Azad University, Marand, Iran.
3 Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran.
4 Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
چکیده [English]
Introduction: Doxorubicin (DOX) is an effective chemotherapy treatment for various cancers, but its use has been restricted due to cardiotoxicity effects. Studies about the protective effect of High-Intensity Interval Training (HIIT) against DOX-induced cardiotoxicity and its mechanisms are rare. This study aimed to investigate the protective effect of HIIT against the DOX-induced cardiotoxicity on the level of miR-499 expression which is widely expressed under the physiological conditions in the cardiomyocytes.
Methods: Twenty-four male Wistar rats were randomly assigned into four groups (n=6/group) including DOX (20 mg/kg body weight), HIIT (eight weeks, and seven 4-minutes sets of intervals at 80%–90% of VO2max interspersed with 3 minutes periods at 65%–75% of VO2max), HIIT+DOX and Control groups. The mRNA expression level was determined using the RT-PCR method. One-way analysis of variance followed by Tukey's post hoc test was used for statistical analysis of data (α<0.05).
Results: The results showed that DOX-induction significantly increased the MIR-499 expression in the left ventricular tissue of the rats’ heart (P<0.05). Also, the expression level of MIR-499 was increased after exercise, but this difference was not statistically significant. Exercise before the DOX-induction also led to a significant reduction of MIR-499 expression in the HIIT+ DOX group compared with the DOX group (P<0.05).
Conclusion: Therefore, performing HIIT before DOX induction can reduce the changes in MIR-499 expression caused by DOX. Therefore, HIIT could be a proper strategy for protecting the heart against DOX-induced cardiotoxicity by reducing MIR-499 expression.
کلیدواژه‌ها [English]
- Cardiotoxicity
- Doxorubicin
- interval training
- MiR-499
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