تأثیر محافظتی تمرین تناوبی هوازی با شدت بالا در مقابل سمیت قلبی ناشی از دوکسوروبیسین در رت‌ها

Khadijeh Ebrahimi1 0000-0003-2819-2385
, Siroos Choobineh 2 0000-0003-4466-0986
, Reza Badalzadeh 3
, Rahman Soori 2
1- دانشجوی دوره دکتری رشته فیزیولوزی ورزشی قلب و عروق و تنفس، پردیس بین المللی ارس دانشگاه تهران، جلفا، ایران.
2- دانشیار، دانشكده تربيت بدني و علوم ورزشي دانشگاه تهران، تهران، ايران.
3- دانشیار، مركز تحقيقات پزشکی مولکولی و مرکز تحقیقات كاربرديي دارويي دانشگاه علوم پزشكي تبريز، تبریز، ایران
2- دانشیار، دانشكده تربيت بدني و علوم ورزشي دانشگاه تهران، تهران، ايران.

چکیده


مقدمه: استفاده بالینی از دوکسوروبیسین (Doxorubicin)) DOX)، که داروی پرکاربردی در درمان انواع سرطان است، بدلیل سمیت قلبی محدود شده است. با وجود توجه فزاینده به نقش محافظتی فعالیت ورزشی بویژه استقامتی با شدت متوسط در مهار سمیت قلبی ناشی از DOX، مطالعات محدودی در مورد تمرین تناوبی هوازی با شدت بالا (AIT (Aerobic High-Intensity Interval Training)) و مکانیسمهای آن در این زمینه صورت گرفته است. بنابراین، هدف از تحقیق حاضر بررسی تأثیر محافظتی AIT در مقابل تغییرات بیان PGC-1α ناشی از DOX در سلولهای قلبی رتها است.

مواد و روش‌ها: رت‌‌های ویستار نر به طور تصادفی به چهار گروه (هر گروه=6) تقسیم شدند: 1) Control؛ 2) DOX (20 میلیگرم/کیلوگرم وزن بدن، داخل صفاقی)؛ 3) AIT (8 هفته، 7 ست 4 دقیقهای با 80-90 درصد VO2max مجزا شده با دورههای 3 دقیقهای 65–75 درصد VO2max)؛ و 4)AIT+DOX . بررسی میزان بیان PGC-1α با روش RT-PCR انجام شد. از تجزیه و تحلیل واریانس یک طرفه و سپس آزمون تعقیبی توکی برای بررسی آماری دادهها استفاده گردید (α>0/05).

نتایج: القای DOX میزان بیان PGC-1α را در بافت قلب کاهش میدهد (05/0>P). میزان بیان PGC-1α نیز پس از AIT افزایش یافت (05/0>P). همچنین، AIT قبل از القای DOX نیز موجب افزایش میزان بیان PGC-1α در گروهAIT+DOX  نسبت به گروه DOX گردید (05/0>P). بنابراین، AIT میتواند موجب مهار تغییرات بیان PGC-1α ناشی از تزریق DOX شود.

نتیجه‌گیری: AIT به عنوان استراتژی غیردارویی مناسب میتواند از قلب در برابر سمیت قلبی ناشی از القای DOX محافظت کند.


واژه های کلیدی


دوکسوروبیسین؛ تمرین تناوبی؛ سمیت قلبی؛ PGC-1α

تمام متن:

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مراجع


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Protective Effect of Aerobic High-Intensity Interval Training Against Doxorubicin-Induced Cardiotoxicity in Rats

Khadijeh Ebrahimi1*, Siroos Choobineh2*, Reza Badalzadeh3, Rahman Soori2

Dept. of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tehran, Aras International Campus, Tehran, Iran.

Dept. of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran.

Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz.

Received: 4 October 2018, Accepted: 23 November 2018

Abstract:

Introduction: Clinical use of Doxorubicin (DOX), a widely useful drug for the treatment of various cancers, is limited by the cardiotoxicity. Despite the growing attention to the protective role of exercise activity, especially moderate endurance exercises against the DOX-induced cardiotoxicity, few studies have focused on aerobic high-interval interval training (AIT) and its mechanisms. Therefore, the purpose of this study was to investigate the protective effect of AIT against the DOX-induced changes in the PGC-1α mRNA levels in the cardiomyocytes of rats.

Methods: 24 male Wistar rats were randomly assigned into four groups (n=6/groups): 1) Control; 2) DOX (20 mg/kg body weight)/; 3) AIT (7 sets of 4 min intervals at 80%–90% VO2max interspersed with 3 min periods of 65%–75% VO2max, for 8 weeks before DOX-injection); and 4) AIT + DOX. The mRNA levels also were determined using RT-PCR. For statistical analysis of data, One-way analysis of variance and Tukey's post hoc test were used (α<0.05).

Results: DOX-treatment significantly decreased the expression of PGC-1α in the DOX group compared to the Control group (P < 0.05). Also, the expression of PGC-1α significantly increased in the AIT group compared to the Control group (P < 0.05). AIT before DOX-induction also significantly increased the expression of PGC-1α in the AIT+DOX group compared to the DOX group (P < 0.05). AIT could inhibit the DOX-induced changes in the PGC-1α mRNA levels in the cardiomyocytes of rats.

Conclusion: AIT could be a good non-prescriptive strategy for preventing of DOX-induced cardiotoxicity.

Keywords: Doxorubicin, Interval training, Cardiotoxicity, PGC-1α.

Conflict of Interest: No

*Corresponding author: K. Ebrahimi, Email: ebrahimi_kh@ut.ac.ir

**Corresponding author: S.Choobine, Email: sirooscc@gmail.com

Citation: Ebrahimi K, Choobineh S, Badalzadeh R, Soori R. Protective Effect of Aerobic High-Intensity Interval Training Against Doxorubicin-Induced Cardiotoxicity in Rats. Journal of Knowledge & Health 2018;13(3):41-48.




DOI: 10.22100/jkh.v13i3.2040

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