ورزش و علوم زیست حرکتی

ورزش و علوم زیست حرکتی

تأثیر تمرین هوازی بر بیان برخی ژن های پرو و آنتی آپوپتوتیک میوکارد رت ها پس از ترک مت آمفتامین

نوع مقاله : مقاله پژوهشی

نویسندگان
1 دانشجوی دکتری، گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه رازی، کرمانشاه، ایران
2 دانشیار، گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه رازی، کرمانشاه، ایران
3 استادیار، مرکز تحقیقات فیزیولوژی ورزش، پژوهشکده سبک زندگی، دانشگاه علوم پزشکی بقیه الله، تهران، ایران
4 استادیار، گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه رازی، کرمانشاه، ایران
چکیده
مقدمه و هدف:مصرف مت ­آمفتامین منجر به آسیب ­های سلولی متعددی می­ شود. مطالعه حاضر با هدف بررسی تاثیر شش هفته تمرین هوازی بر بیان ژن­ های پرو و آنتی آپوپتوتیک میوکارد رت ­ها پس از ترک مت ­آمفتامین انجام شد.
مواد و روش­ ها: تعداد 32 سر رت نر نژاد ویستار بطور تصادفی به چهار گروه (گروه مت ­آمفتامین، گروه مت­ آمفتامین سپس ترک، گروه مت­آمفتامین سپس ترک سپس تمرین و گروه مت ­آمفتامین سپس ترک سپس زندگی عادی و بدون مداخله (گروه کنترل)) تقسیم شدند. مت ­آمفتامین  بصورت درون صفاقی و در هفته اول مقدار 10 میلی‌گرم بر کیلوگرم و دو بار در روز به رت ­ها تزریق شد. از هفته دوم تا ششم، هر هفته، 1 میلی‌گرم بر کیلوگرم به دوز تزریقی اضافه شد. پروتکل ورزشی پژوهش حاضر اجرای 6 هفته تمرین هوازی روی تردمیل با شدت متوسط و به مدت 60 دقیقه در روز و 5 روز در هفته بود. سطوح بیان ژن­ های BAX و Bcl-2 در بافت میوکارد رت­ها مورد ارزیابی قرار گرفت. داده­ ها با آزمون آماری آنالیز واریانس یک طرفه و در سطح معنی­ داری 0.05>P تجزیه و تحلیل شدند.
یافته­ ها: مت ­آمفتامین باعث افزایش آپوپتوز از طریق افزایش بیان ژن BAX، کاهش بیان ژن Bcl-2 و نسبت BAX/Bcl-2 شد. ترک مصرف مت ­آمفتامین و تمرینات هوازی باعث کاهش معنی ­داری در بیان ژن BAX، نسبت BAX/Bcl-2 و افزایش در بیان ژن Bcl-2 شد (0.05>P).
بحث و نتیجه­‌گیری: مصرف مت ­آمفتامین می ­تواند بیان برخی ژن­ های پروآپوپتوتیک را افزایش و بیان ژن­ های ضدآپوپتوزی را در میوکارد کاهش دهد. از طرفی ترک مصرف مت­ آمفتامین و تمرینات هوازی می ­تواند روند آپوپتوز را در میوکارد رت­ ها کاهش دهد.
کلیدواژه‌ها

عنوان مقاله English

Effects of aerobic training on the expression of some pro- and anti-apoptotic genes in the myocardium of rats after methamphetamine withdrawal

نویسندگان English

Negin Kordi 1
mohammad azizi 2
Mohammad Samada 3
Worya Tahmasebi 4
1 PhD Candidate, Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran
2 Associate Professor, Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran
3 Assistant Professor, Exercise Physiology Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
4 Assistant Professor, Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran
چکیده English

Introduction and Purpose: The use of methamphetamine leads to numerous cell damage. This study aimed to investigate the effect of six weeks of aerobic training on the expression of pro- and anti-apoptotic genes in the myocardium of rats after withdrawal from ethamphetamine.
Materials and Methods: 32 male Wistar rats were randomly assigned to four groups (methamphetamine group, methamphetamine then withdrawal group, methamphetamine then withdrawal then training group and methamphetamine then withdrawal then normal life without intervention group (control group)). Methamphetamine was injected intraperitoneally and in the first week in the amount of 10 mg/kg twice a day. From the second to the sixth week, every week, 1 mg/kg was added to the injection dose. The training protocol includes 6 weeks of aerobic training on a treadmill with moderate intensity for 60 minutes a day and 5 days a week. The expression levels of BAX and Bcl-2 genes were evaluated in rat myocardial tissue. The data were analyzed by one-way analysis of variance at a significance level of P≤0.05.
Results: Methamphetamine increased apoptosis by increasing BAX gene expression, decreasing Bcl-2 gene expression and BAX/Bcl-2 ratio. methamphetamine withdrawal and aerobic training caused a significant decrease in BAX gene expression, BAX/Bcl-2 ratio and an increase in Bcl-2 gene expression (P≤0.05).
Discussion and Conclusion: Methamphetamine use can increase the expression of some pro-apoptotic genes and decrease the expression of myocardial anti-apoptotic genes. On the other hand, methamphetamine withdrawal and aerobic training can reduce the process of apoptosis in the myocardium of rats.

کلیدواژه‌ها English

continuous traning
BAX
Bcl-2
heart
crystal meth
Xu E, Liu J, Liu H, Wang X, Xiong H. Inflammasome activation by methamphetamine potentiates lipopolysaccharide
stimulation of IL-1β production in microglia. Journal of Neuroimmune Pharmacology. 2018;13:237-
53.http://doi.org/10.1007/s11481-018-9780-y.
2. Kelly KA, Miller DB, Bowyer JF, O’Callaghan JP. Chronic exposure to corticosterone enhances the neuroinflammatory
and neurotoxic responses to methamphetamine. Journal of neurochemistry. 2012;122(5):995-1009. http://doi.org/
10.1111/j.1471-4159.2012.07864.x.
3. Akhgari M, Mobaraki H, Etemadi-Aleagha A. Histopathological study of cardiac lesions in methamphetamine poisoningrelated deaths. DARU Journal of Pharmaceutical Sciences. 2017;25:1-9. http://doi.org/10.1111/j.1471-
4159.2012.07864.x.
4. Galinato MH, Orio L, Mandyam CD. Methamphetamine differentially affects BDNF and cell death factors in
anatomically defined regions of the hippocampus. Neuroscience. 2015;286:97-108.
http://doi.org/10.1016/j.neuroscience.2014.11.042.
5. Luo Y, He H, Ou Y, Zhou Y, Fan N. Elevated serum levels of TNF‐α, IL‐6, and IL‐18 in chronic methamphetamine
users. Human Psychopharmacology: Clinical and Experimental. 2022;37(1):e2810. http://doi.org/10.1002/hup.2810.
6. Communal C, Sumandea M, de Tombe P, Narula J, Solaro RJ, Hajjar RJ. Functional consequences of caspase activation
in cardiac myocytes. Proceedings of the National Academy of Sciences. 2002;99(9):6252-6.
http://doi.org/10.1073/pnas.09202299.
7. Parrish AB, Freel CD, Kornbluth S. Cellular mechanisms controlling caspase activation and function. Cold Spring
Harbor perspectives in biology. 2013;5(6):a008672. http://doi.org/10.1101/cshperspect.a008672.
8. Marzetti E, Privitera G, Simili V, Wohlgemuth SE, Aulisa L, Pahor M, et al. Multiple pathways to the same end:
mechanisms of myonuclear apoptosis in sarcopenia of aging. The Scientific World Journal. 2010;10:340-9. http://doi.org/
10.1100/tsw.2010.27.
9. Gross A. BCL-2 family proteins as regulators of mitochondria metabolism. Biochimica et Biophysica Acta (BBA)-
Bioenergetics. 2016;1857(8):1243-6. http://doi.org/10.1016/j.bbabio.2016.01.017.
10. Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for
physiology and therapy. Nature reviews Molecular cell biology. 2014;15(1):49-63. http://doi.org/10.1038/nrm3722.
11. Krasnova IN, Ladenheim B, Cadet JL. Amphetamine induces apoptosis of medium spiny striatal projection neurons via
the mitochondria‐dependent pathway. The Federation of American Societies for Experimental Biology journal.
2005;19(7):1-22. http://doi.org/10.1096/fj.04-2881fje.
12. Shan K, Kurrelmeyer K, Seta Y, Wang F, Dibbs Z, Deswal A, et al. The role of cytokines in disease progression in heart
failure. Current Opinion in Cardiology.1997; 12(3):218-23. http://doi.org/10.1097/00001573-199705000-00002.
13. Marshall D, Ssck MN. Apoptosis: a pivotal event or an epiphenomenon in the pathophysiology of heart failure?.
Heart. 2000; 84(4): 355–356. http://doi.org/10.1136/heart.84.4.355.
14. Akbar AY, Cui ZY, Hsu CJ, Li YZ, Rahman FF, Xia C, Yang AL, Lee SD. Anti-apoptotic and anti-fibrotic efficacy of
exercise training in hypertensive hearts: A systematic review. Frontiers in Cardiovascular Medicine. 2023;10:1138705.
http://doi.org/10.3389/fcvm.2023.1138705.
15. Aro J, Tokola H, Ronkainen VP, Koivisto E, Tenhunen O, Ilves M, et al. Regulation of cardiac melusin gene expression
by hypertrophic stimuli in the rat. Acta Physiologica. 2013;207(3):470-84. http://doi.org/10.1111/apha.12044.
16. Soori R, Ghram A, Zare Shahneh M, Choobineh S, Costa PB, Voltarelli FA. Effects of high intensity interval training and
aging on cardiac muscle apoptosis markers in C57BL/6 Mice. Sport Sciences for Health. 2021;17:173-9.
http://doi.org/10.1007/s11332-020-00670-2.
17. Jahani M, Matin Homaie H, Farzanegi P. Effect of Continuous and Interval Exercise on the Necroptosis and Apoptosis of
Endoplasmic Reticulum Proteins in the Heart of Diabetic Wistar Rats. Journal of Ilam University of Medical Sciences.
2020;28(5):53-63. [In Persian]. http://doi.org/10.29252/sjmu.28.5.53
18. Mirdar S, Moghadasi N, Hamidain G. Effect of High Intensity Interval Training on Heart Apoptosis of Young RatsThe
Effect of High Intensity Interval Training on Heart Apoptosis of Young Rats. Journal of Sport Biosciences.
2019;11(1):49-61. [In Persian]. http://doi.org/10.22059/jsb.2018.260980.1285.
19. Liang L-Y, Wang M-M, Liu M, Zhao W, Wang X, Shi L, et al. Chronic toxicity of methamphetamine: oxidative
remodeling of pulmonary arteries. Toxicology In Vitro. 2020;62:104668 .http://doi.org/10.1016/j.tiv.2019.104668.
20. Rezaeian L, Kalalian-Moghaddam H, Mohseni F, Khaksari M, Rafaiee R. Effects of berberine hydrochloride on
methamphetamine-induced anxiety behaviors and relapse in rats. Iranian Journal of Basic Medical Sciences. 2020
Nov;23(11):1480. http://doi.org/10.22038/ijbms.2020.47285.10884.
21. Ávila RA, Rossi EM, de Carvalho GM, Krause M, Leopoldo AS, Carneiro MTW, et al. Moderate‐intensity aerobic
training reduces cardiac damage attributable to experimental iron overload in rats. Experimental Physiology.
2021;106(8):1772-84. http://doi.org/10.1113/EP089429.
22. Shin EJ, Tran HQ, Nguyen PT, Jeong JH, Nah SY, Jang CG, Nabeshima T, Kim HC. Role of mitochondria in
methamphetamine-induced dopaminergic neurotoxicity: involvement in oxidative stress, neuroinflammation, and proapoptosis—a review. Neurochemical research. 2018;43:66-78. http://doi.org/10.1007/s11064-017-2318-5.
23. Pillai S, Cesarz B, Boulware C, Khan A. Hypotension, severe hyperthermia (42 C), rhabdomyolysis, and disseminated
intravascular coagulation induced by lethal dose of methamphetamine. Cureus. 2019;11(7).
http://doi.org/10.7759/cureus.5245.
24. Wenlock MC, Potter T, Barton P, Austin RP. A method for measuring the lipophilicity of compounds in mixtures of 10.
journal of Biomolecular screening. 2011;16(3):348-55. http://doi.org/10.1177/1087057110396372.
25. Liou C-M, Tsai S-C, Kuo C-H, Williams T, Ting H, Lee S-D. Chronic methamphetamine exposure induces cardiac fasdependent and mitochondria-dependent apoptosis. Cardiovascular toxicology. 2014 ;14(2):134-44 .
http://doi.org/10.1007/s12012-013-9237-8.
26. Sun X, Wang Y, Xia B, Li Z, Dai J, Qiu P, et al. Methamphetamine produces cardiac damage and apoptosis by
decreasing melusin. Toxicology and applied pharmacology. 2019;378:114543. http://doi.org/10.1016/j.taap.2019.03.015.
27. Unsöld B, Kaul A, Sbroggiò M, Schubert C, Regitz-Zagrosek V, Brancaccio M, et al. Melusin protects from cardiac
rupture and improves functional remodelling after myocardial infarction. Cardiovascular research. 2014;101(1):97-107.
http://doi.org/10.1093/cvr/cvt235.
28. Gu R, Zheng D, Bai J, Xie J, Dai Q, Xu B. Altered melusin pathways involved in cardiac remodeling following acute
myocardial infarction. Cardiovascular Pathology. 2012;21(2):105-11. http://doi.org/10.1016/j.carpath.2011.03.002.
29. Yang G, Zeng X, Li J, Leung C-K, Zhang D, Hong S, et al. Protective effect of gastrodin against methamphetamineinduced autophagy in human dopaminergic neuroblastoma SH-SY5Y cells via the AKT/mTOR signaling pathway.
Neuroscience Letters. 2019;707:134287. http://doi.org/10.1016/j.neulet.2019.134287.
30. Maherinia H, Peeri M, Azarbayjani MA, Delfan M. Aerobic exercise training combined with probiotic supplement
improves antioxidant defence of cardiomyocytes by regulating Nrf2 and caspase3 gene expression in type 2 diabetic rats.
Comparative Exercise Physiology. 2022;18(3):255-63. http://doi.org/10.3920/CEP200089.
31. Gonçalves J, Martins T, Ferreira R, Milhazes N, Borges F, Ribeiro CF, Malva JO, Macedo TR, Silva AP.
Methamphetamine‐induced early increase of il‐6 and tnf‐α mrna expression in the mouse brain. Annals of the New
York Academy of Sciences. 2008 ;1139(1):103-11. http://doi.org/10.1196/annals.1432.043.
32. Coelho-Santos V, Gonçalves J, Fontes-Ribeiro C, Silva AP. Prevention of methamphetamine-induced microglial cell
death by TNF-α and IL-6 through activation of the JAK-STAT pathway. Journal of neuroinflammation. 2012;9(1):1-14.
http://doi.org/10.1186/1742-2094-9-103.
33. Kordi N, Shafiee N, Mirzaei S, Minavand K, Heidari N. The effect of continuous and interval cardiac rehabilitation
exercise training on tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) in patients
with coronary artery bypass graft. Journal of Isfahan Medical School. 2018;36(486):737-42. [In Persian]
http://doi.org/10.22122/JIMS.V36I486.10019.
34. Mohammad K, Mateen Homaie H, Farzanegi P. The effect of aerobic exercise with pistachio skin extract on the
expression of Bax, caspase-3 and Bcl-2 in heart tissue of fat-fed rats. Kashan University of Medical SciencesJ ournal
(FEYZ). 2022;26(5):521-9. [In Persian]. http://doi.org/10.48307/FMSJ.2022.26.5.521.
35. Luan X, Chen H, Qiu H, Shen H, Zhao K, Ren W, et al. Association between serum malondialdehyde levels and
depression during early methamphetamine withdrawal. Neuroscience letters. 2018;687:22-5.
http://doi.org/10.1016/j.neulet.2018.09.021.
36. Ansley DM, Wang B. Oxidative stress and myocardial injury in the diabetic heart. The Journal of pathology.
2013;229(2):232-41. http://doi.org/10.1002/path.4113.
37. Toborek M, Seelbach MJ, Rashid CS, András IE, Chen L, Park M, Esser KA. Voluntary exercise protects against
methamphetamine-induced oxidative stress in brain microvasculature and disruption of the blood–brain barrier.
Molecular neurodegeneration. 2013;8:1-1. http://doi.org/10.1186/1750-1326-8-22.
38. Wang J, Lu C, Zheng L, Zhang J. Peripheral inflammatory biomarkers of methamphetamine withdrawal patients based
on the neuro-inflammation hypothesis: the possible improvement effect of exercise. Frontiers in Psychiatry.
2021;12:795073. http://doi.org/10.3389/fpsyt.2021.795073.

  • تاریخ دریافت 01 شهریور 1402
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  • تاریخ پذیرش 27 مهر 1402