اثر شش هفته تمرین تناوبی با شدت بالا همراه با مکمل یاری عصاره‌ی زالزالک بر تغییرات شاخص‌های BAX/Bcl-2 بافت هیپوکمپ موش‌های صحرایی نر نژاد ویستار سالمند

نوع مقاله : Original Article(s)

نویسندگان

1 کارشناسی ارشد، گروه فیزیولوژی ورزشی، دانشکده‌ی علوم ورزشی، دانشگاه شهید چمران اهواز، اهواز، ایران

2 استادیار، گروه فیزیولوژی ورزشی، دانشکده‌ی علوم ورزشی، دانشگاه شهید چمران اهواز، اهواز، ایران

3 استادیار، واحد تحقیقات سلامت از طریق ورزش و زندگی فعال (HEAL)، دانشکده‌ی پزشکی و علوم بهداشتی، دانشگاه صباح مالزی و گروه علوم زیست‌پزشکی، دانشکده‌ی پزشکی و علوم بهداشتی، دانشگاه صباح مالزی، جالان UMS، کوتا کینابالو، صباح، مالزی

چکیده

مقاله پژوهشی




مقدمه: سالمندی، پدیده‌ای پیچیده و چند عاملی است که با کاهش تدریجی اعمال فیزیولوژیکی در اندام‌های مختلف مشخص شده و سیستم عصبی مرکزی و ناحیه‌ی هیپوکمپ به صورت قابل توجهی تحت تأثیر عوارض سالمندی نظیر آپوپتوز قرار می‌گیرند. هم‌افزایی اثرات فعالیت بدنی به همراه آنتی‌اکسیدان‌های طبیعی نظیر زالزالک برای محافظت از آسیب مغزی در برابر فرایند آپوپتوز ممکن است کلید مهار یا کاهش آپوپتوز سلول‌های عصبی در فرایند سالمندی باشد. لذا هدف از مطالعه‌ی حاضر، بررسی اثر تمرین تناوبی با شدت بالا همراه با مکمل یاری عصاره‌ی زالزالک بر تغییرات شاخص‌های BAX/Bcl-2 بافت هیپوکمپ موش‌های صحرایی سالمند می‌باشد.
روش‌ها: در تحقیق تجربی حاضر، 30 سر رت صحرایی نر نژاد ویستار با 22 ماه سن به صورت تصادفی به 5 گروه 6‌تایی شامل: جوان، سالمند، سالمند/تمرین، سالمند/عصاره و سالمند/عصاره/تمرین تقسیم شدند. در گروه‌هایی که عصاره‌ی زالزالک استفاده می‌کنند، پس از جلسات تمرینی مقدار 100 میلی‌گرم/کیلوگرم عصاره را به صورت گاواژ دریافت می‌کردند. پروتکل تمرین تناوبی با شدت بالا به مدت شش هفته و با شدت 100-80 درصد سرعت بیشینه بود. پس از بافت‌برداری، مقادیر پروتئین‌های BAX/Bcl-2 با استفاده از روش وسترن بلات اندازه‌گیری شد. از آزمون one-way ANOVA و سپس آزمون تعقیبی Tukey برای بررسی متغیرهای پژوهش استفاده گردید.
یافته‌ها: نتایج پژوهش حاضر نشان داد که سالمندی سبب کاهش معنی‌داری در متغیر Bcl-2 شده و در متغیر BAX افزایش معنی‌داری را نشان می‌دهد (0/001 = P). همچنین هم تمرینتناوبی با شدت بالا و هم مصرف عصاره‌ی زالزالک باعث افزایش معنی‌داری در مقادیر Bcl-2 (به ترتیب، 0/031 = P و 0/011 = P) و کاهش معنی‌داری در پروتئین BAX شد (به ترتیب، 0/003 = P و 0/016 = P). همچنین نتایج نشان داد که هم‌افزایی اثرات تمرین تناوبی با شدت بالا در گروه سالمند/عصاره/تمرین، به ترتیب سبب افزایش و کاهش معنی‌دار متغیرهای Bcl-2 و BAX نسبت به گروه‌های سالمند/تمرین و سالمند/عصاره می‌شود (0/05 > P).
نتیجه‌گیری: با توجه به نتایج این پژوهش می‌توان اظهار داشت که هم‌افزایی اثرات مفید فعالیت بدنی از نوع تناوبی با شدت بالا به همراه مصرف عصاره‌ی زالزالک، در افزایش متغیر Bcl-2 و کاهش متغیر BAX، احتمالاً می‌تواند نقش مهمی در مهار فرایند آپوپتوز در بافت هیپوکامپ موش‌های صحرایی سالمند ایفا کند و احتمالاً می‌تواند به عنوان یک راهبرد غیردارویی امیدوارکننده باشد.

تازه های تحقیق

فاطمه کیانی زادگان: Google Scholar

محمد رمی: Google Scholar, PubMed

علی اکبر علی زاده: Google Scholar, PubMed

دی ماریاما آوانگ داود: Google Scholar, PubMed

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

The Effect of Six Weeks of High-Intensity Interval Training with Hawthorn Extract Supplementation on the Changes of BAX/Bcl-2 Indices in the Hippocampus Tissue of Aged Male Wistar Rats

نویسندگان [English]

  • Fatemeh Kianizadegan 1
  • Mohammad Rami 2
  • Aliakbar Alizadeh 2
  • D. Maryama Awang Daud 3
1 MSc, Department of Sport Physiology, School of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
2 Assistant Professor, Department of Sport Physiology, School of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
3 Assistant Professor, Health Through Exercise and Active Living (HEAL) Research Unit, School of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia and Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Malaysia Sabah, Jalan UMS, Kota Kinabalu 88450, Sabah, Malaysia
چکیده [English]

Background: Aging is a complex and multifactorial phenomenon characterized by a gradual decrease in physiological functions in various organs. The central nervous system and the hippocampus are significantly affected by the effects of aging, such as apoptosis. The synergistic effects of physical activity and natural antioxidants such as hawthorn to protect brain damage against apoptosis may be the key to inhibiting or reducing the apoptosis of nerve cells in the aging process. Therefore, this study aims to investigate the effect of high-intensity interval training with hawthorn extract supplementation on the changes of BAX/Bcl-2 indices in the hippocampus tissue of aged rats.
Methods: In this experimental research, 30 male Wistar field rats 22 months of age were randomly divided into five groups of six, including young, elderly, elderly/exercise, elderly/extract, and elderly/extract/exercise. In the groups that used hawthorn extract, they received 100 mg/kg of the extract by gavage after training sessions. The high-intensity interval training protocol was for six weeks with an intensity of 80-100% of maximum speed. After tissue removal, BAX/Bcl-2 protein levels were measured using the western blot method. One-way ANOVA and Tukey's post hoc test were used to examine the research variables.
Findings: The results of the present study showed that aging caused a significant decrease in the Bcl-2 variable and a significant increase in the BAX variable (P = 0.001). Also, the results of this research showed that both high-intensity interval training and hawthorn extract consumption caused a consequential advance in Bcl-2 values (respectively, P = 0.031 and P = 0.011) and a significant decrease in BAX protein (P = 0.003 and P = 0.016, respectively). In addition, the results of this research showed that the synergistic effects of high-intensity interval training in the elderly/extract/exercise group caused a significant increase and decrease in Bcl-2 and BAX variables, respectively, compared to the elderly/exercise and elderly/extract groups (P < 0.05).
Conclusion: According to the results of this research, it can be stated that the synergy of the beneficial effects of high-intensity intermittent physical activity along with the consumption of hawthorn extract in increasing the Bcl-2 variable and decreasing the BAX variable can probably play a consequential role in inhibiting the apoptosis process in the rat hippocampus tissue and can probably be a promising non-pharmacological strategy.

کلیدواژه‌ها [English]

  • Aging
  • Apoptosis
  • Hippocampus
  • Exercise

مراجع

  1. Carver L. Biohacking and aging technology–a primer. 1st In: An interdisciplinary approach to aging, biohacking and technology. London, UK: Routledge; 2024. p. 6-23.
  2. Fuso A. Aging and disease: the epigenetic bridge. Epigenetics in Human Disease: Elsevier; 2024. p. 1177-218.
  3. Amirazodi M, Mehrabi A, Rajizadeh MA, Bejeshk MA, Esmaeilpour K, Daryanoosh F, et al. The effects of combined resveratrol and high intensity interval training on the hippocampus in aged male rats: an investigation into some signaling pathways related to mitochondria. Iran J Basic Med Sci 2022; 25(2): 254-62.
  4. Blinkouskaya Y, Caçoilo A, Gollamudi T, Jalalian S, Weickenmeier J. Brain aging mechanisms with mechanical manifestations. Mech Ageing Dev 2021; 200: 111575.
  5. Kim JH, Liu QF, Urnuhsaikhan E, Jeong HJ, Jeon MY, Jeon S. Moderate-intensity exercise induces neurogenesis and improves cognition in old mice by upregulating hippocampal hippocalcin, otub1, and spectrin-α. Mol Neurobiol 2019;56:3069-78.
  6. Miller D, O’callaghan J. Aging, stress and the hippocampus. Ageing Res Rev 2005; 4(2): 123-40.
  7. Cao L, Jiao X, Zuzga DS, Liu Y, Fong DM, Young D, et al. VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 2004; 36(8): 827-35.
  8. Kuhn HG, Dickinson-Anson H, Gage FH. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 1996; 16(6): 2027-33.
  9. Schroer J, Warm D, De Rosa F, Luhmann HJ, Sinning A. Activity-dependent regulation of the BAX/BCL-2 pathway protects cortical neurons from apoptotic death during early development. Cell Mol Life Sci 2023; 80(6): 175.
  10. Pollack M, Phaneuf S, Dirks A, Leeuwenburgh C. The role of apoptosis in the normal aging brain, skeletal muscle, and heart. Ann N Y Acad Sci 2002; 959: 93-107.
  11. Perry VH. The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun 2004; 18(5): 407-13.
  12. Mattson MP, Magnus T. Ageing and neuronal vulnerability. Nat Rev Neurosci 2006; 7(4): 278-94.
  13. Pemberton JM, Pogmore JP, Andrews DW. Neuronal cell life, death, and axonal degeneration as regulated by the BCL-2 family proteins. Cell Death Differ 2021; 28(1): 108-22.
  14. Huang C-Y, Kuo W-W, Liao H-E, Lin Y-M, Kuo C-H, Tsai F-J, et al. Lumbrokinase attenuates side-stream-smoke-induced apoptosis and autophagy in young hamster hippocampus: correlated with eNOS induction and NFκB/iNOS/COX-2 signaling suppression. Chem Res Toxicol 2013; 26(5): 654-61.
  15. Almeida O, Conde G, Crochemore C, Demeneix B, Fischer D, Hassan A, et al. Subtle shifts in the ratio between pro‐and antiapoptotic molecules after activation of corticosteroid receptors decide neuronal fate. FASEB J 2000; 14(5): 779-90.
  16. Savory J, Rao J, Huang Y, Letada P, Herman M. Age-related hippocampal changes in Bcl-2: Bax ratio, oxidative stress, redox-active iron and apoptosis associated with aluminum-induced neurodegeneration: increased susceptibility with aging. Neurotoxicology 1999; 20(5): 805-17.
  17. Basu A. The interplay between apoptosis and cellular senescence: Bcl-2 family proteins as targets for cancer therapy. Pharmacol Ther 2022; 230: 107943.
  18. Argüelles S, Guerrero‐Castilla A, Cano M, Muñoz MF, Ayala A. Advantages and disadvantages of apoptosis in the aging process. Ann N Y Acad Sci 2019; 1443(1): 20-33.
  19. Barriuso D, Alvarez-Frutos L, Gonzalez-Gutierrez L, Motiño O, Kroemer G, Palacios-Ramirez R, et al. Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence. Int J Mol Sci 2023; 24(7): 6374.
  20. Kalache A, Aboderin I, Hoskins I. Compression of morbidity and active ageing: key priorities for public health policy in the 21st century. Bull World Health Organ 2002; 80(3): 243-4.
  21. Eckstrom E, Neukam S, Kalin L, Wright J. Physical activity and healthy aging. Clin Geriatr Med 2020; 36(4): 671-83.
  22. Rendeiro C, Rhodes JS. A new perspective of the hippocampus in the origin of exercise–brain interactions. Brain Struct Funct 2018; 223(6): 2527-45.
  23. Gao Y, Syed M, Zhao X. Mechanisms underlying the effect of voluntary running on adult hippocampal neurogenesis. Hippocampus 2023; 33(4): 373-90.
  24. Midoen YH, Ilyas S, Santoso P, Situmorang PC. Effect of maximal physical exercise on apoptosis via cytochrome c in hippocampus cells after administration of Vitis gracilis Wall. J Pharm Pharmacogn Res 2023; 11(2): 297-307.
  25. Coates AM, Joyner MJ, Little JP, Jones AM, Gibala MJ. A perspective on high-intensity interval training for performance and health. Sports Medicine 2023; 53(Suppl 1): 85-96.
  26. Akkaya EC, Koc B, Dalkiran B, Calis G, Dayi A, Kayatekin BM. High-intensity interval training ameliorates spatial and recognition memory impairments, reduces hippocampal TNF-alpha levels, and amyloid-beta peptide load in male hypothyroid rats. Behav Brain Res 2024; 458: 114752.
  27. Barmar ZT, Cheragh-Birjandi S, Rezaeian N. The effect of high-intensity interval training and curcumin supplementation on apoptosis indicators such as TNF-α, nfkb and fas on hippocampal neurotoxicity caused by hydrogen peroxide consumption in male rats. Journal of Applied Health Studies in Sport Physiology 2023; 10(2): 54-67.
  28. Rocha-Gomes A, e Castro TPA, Almeida PR, Leme PSBP, da Silva AA, Riul TR, et al. High-intensity interval training improves long-term memory and increases hippocampal antioxidant activity and BDNF levels in ovariectomized Wistar rats. Behav Brain Res 2023; 453: 114605.
  29. Shirpour S, Azarbayjani MA, Peeri M, Farzanegi P. Effect of high intensity interval training with curcumin on gene expression of Bax, Bcl-2, and Caspase-3 in aged female rat hepatocytes. Report of Health Care 2017; 3(3): 8-14.
  30. Novoa U, Arauna D, Moran M, Nuñez M, Zagmutt S, Saldivia S, et al. High‐intensity exercise reduces cardiac fibrosis and hypertrophy but does not restore the nitroso‐redox imbalance in diabetic cardiomyopathy. Oxid Med Cell Longev 2017; 2017(1): 7921363.
  31. Lei Z, Mozaffaritabar S, Kawamura T, Koike A, Kolonics A, Kéringer J, et al. The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice. Heliyon 2024; 10(2): e24421.
  32. Gibala MJ, Little JP, MacDonald MJ, Hawley JA. Physiological adaptations to low‐volume, high‐intensity interval training in health and disease. J Physiol 2012; 590(5): 1077-84.
  33. Rajizadeh MA, Najafipour H, Bejeshk MA. An updated comprehensive review of plants and herbal compounds with antiasthmatic effect. Evidence‐Based Complementary and Alternative Medicine 2024; 2024: 1-36.
  34. Nazhand A, Lucarini M, Durazzo A, Zaccardelli M, Cristarella S, Souto SB, et al. Hawthorn (Crataegus spp.): An updated overview on its beneficial properties. Forests 2020; 11(5): 564.
  35. Deniz GY, Geyikoglu F, Erol HS, Aslan M. The effectiveness of Hawthorn (Ws-1442 Standardized Crataegus oxycantha Extract) against alcohol-induced brain injury in rat; Its Underlying Potential Mechanisms. 2024.
  36. Elango C, Jayachandaran KS, Devaraj SN. Hawthorn extract reduces infarct volume and improves neurological score by reducing oxidative stress in rat brain following middle cerebral artery occlusion. Int J Dev Neurosci 2009; 27(8): 799-803.
  37. Zarrinkalam E, Ranjbar K, Salehi I, Kheiripour N, Komaki A. Resistance training and hawthorn extract ameliorate cognitive deficits in streptozotocin-induced diabetic rats. Biomed Pharmacother 2018; 97: 503-10.
  38. Ganji A, Salehi I, Sarihi A, Shahidi S, Komaki A. Effects of Hypericum Scabrum extract on anxiety and oxidative stress biomarkers in rats fed a long-term high-fat diet. Metab Brain Dis 2017; 32(2): 503-11.
  39. Elango C, Devaraj SN. Immunomodulatory effect of Hawthorn extract in an experimental stroke model. J Neuroinflammation 2010; 7: 97.
  40. Soori R, Amini AA, Choobineh S, Eskandari A, Behjat A, Ghram A, et al. Exercise attenuates myocardial fibrosis and increases angiogenesis-related molecules in the myocardium of aged rats. Arch Physiol Biochem 2022; 128(1): 1-6.
  41. Deng H, Yue JK, Zusman BE, Nwachuku EL, Abou-Al-Shaar H, Upadhyayula PS, et al. B-cell lymphoma 2 (Bcl-2) and regulation of apoptosis after traumatic brain injury: A clinical perspective. Medicina (Kaunas) 2020; 56(6): 300.
  42. Kim S-E, Ko I-G, Kim B-K, Shin M-S, Cho S, Kim C-J, et al. Treadmill exercise prevents aging-induced failure of memory through an increase in neurogenesis and suppression of apoptosis in rat hippocampus. Exp Gerontol 2010; 45(5): 357-65.
  43. Lin J-Y, Kuo W-W, Baskaran R, Kuo C-H, Chen Y-A, Chen WS-T, et al. Swimming exercise stimulates IGF1/PI3K/Akt and AMPK/SIRT1/PGC1α survival signaling to suppress apoptosis and inflammation in aging hippocampus. Aging (albany NY) 2020; 12(8): 6852-64.
  44. Culmsee C, Landshamer S. Molecular insights into mechanisms of the cell death program: role in the progression of neurodegenerative disorders. Curr Alzheimer Res 2006; 3(4): 269-83.
  45. 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.
  46. Song W, Kwak H-B, Lawler JM. Exercise training attenuates age-induced changes in apoptotic signaling in rat skeletal muscle. Antioxid Redox Signal 2006; 8(3-4): 517-28.
  47. Tan R-f, Xia A-h, Wu X-g, Cao N-n, Li M-m, Zhang T-g, et al. Total Flavone of Hawthorn Leaf inhibits neuronal apoptosis in brain tissue of rat models of chronic cerebral ischemia. Chinese Journal of Tissue Engineering Research 2014; 18(49): 7879.
  48. Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging 2018; 13: 757-72.
  49. Brokatzky D, Dörflinger B, Haimovici A, Weber A, Kirschnek S, Vier J, et al. A non‐death function of the mitochondrial apoptosis apparatus in immunity. EMBO J 2019; 38(11): e100907.
  50. Thirupathi A, Pinho RA, Chang Y-Z. Physical exercise: An inducer of positive oxidative stress in skeletal muscle aging. Life Sci 2020; 252: 117630.
  51. Ding Y, Chang C, Xie L, Chen Z, Ai H. Intense exercise can cause excessive apoptosis and synapse plasticity damage in rat hippocampus through Ca2+ overload and endoplasmic reticulum stress-induced apoptosis pathway. Chin Med J (Engl) 2014; 127(18): 3265-71.
  52. Krüger K, Mooren FC. Exercise-induced leukocyte apoptosis. Exerc Immunol Rev 2014; 20: 117-34.
  53. Novoa U, Arauna D, Moran M, Nuñez M, Zagmutt S, Saldivia S, et al. High-intensity exercise reduces cardiac fibrosis and hypertrophy but does not restore the nitroso-redox imbalance in diabetic cardiomyopathy. Oxid Med Cell Longev 2017; 2017: 7921363.
مجله دانشکده پزشکی اصفهان
دوره 42، شماره 769
هفته 1، مرداد
مرداد و شهریور 1403
صفحه 450-460

فایل ها

سابقه مقاله

  • تاریخ دریافت: 05 تیر 1403
  • تاریخ پذیرش: 21 مرداد 1403

هم رسانی

ارجاع به این مقاله

آمار