تأثیر هشت هفته تمرین مقاومتی به همراه مکمل‌یاری اسپیرولینا بر مسیر پیام‌رسانی Wnt/ GSK-3β / TSC2/ S6K بافت کلیه رت های نر

نوع مقاله : مقاله پژوهشی Released under (CC BY-NC 4.0) license I Open Access I


1 گروه علوم ورزشی، دانشکده ادبیات و علوم انسانی، دانشگاه خلیج فارس، بوشهر، ایران.

2 گروه فیزیولوژی ورزشی دانشکده ادبیات و علوم انسانی، دانشگاه خلیج فارس، بوشهر، ایران

3 دانشیار، گروه علوم ورزشی، دانشکده ادبیات و علوم انسانی، دانشگاه خلیج فارس، بوشهر، ایران



هدف: سیگنالینگ Wnt یکی از مهم­ترین مسیرهای پیام­رسانی در­گیر در جریان تمرینات مقاومتی بوده که تاثیر مولکولی زیادی در مسیر تکاملی بافت کلیه و بیماری­های این بافت دارد. هدف از تحقیق حاضر بررسی تاثیر هشت هفته تمرین مقاومتی به همراه مکمل‌یاری اسپیرولینا بر مسیر پیام­رسانیWnt/ GSK-3β / TSC2/ S6K  بافت کلیه رت­های نر بود. روش شناسی: پژوهش حاضر از نوع طرح تجربی بود که تعداد 32 سر رت نر جوان با 3 ماه سن و میانگین وزن 20±150 گرم بطور تصادفی در چهار گروه کنترل، تمرین مقاومتی، اسپیرولینا و تعامل تمرین و اسپیرولینا قرار داده­شدند. گروه­های تمرین مقاومتی به به مدت هشت هفته و 5 جلسه در هفته به تمرین مقاومتی پرداختند که تمرین روزانه شامل 3 ست 5 تکراری با 1 دقیقه استراحت بین هر تکرار و 2 دقیقه استراحت بین ست­ها بود و بار تمرین از 30 درصد وزن بدن هر رت در هفته اول شروع و به 100 درصد وزن در هفته پایانی رسید. گروه­های مکمل، مکمل اسپیرولینا را با دوز 200 میلی­گرم به ازای هر کیلو­گرم وزن بدن به مدت هشت هفته مصرف کردند. برای بیان ژن­های مورد مطالعه تحقیق از روش Real-Time PCR استفاده شد. از نرم افزار SPSS نسخه 24 و آمار استنباطی تحلیل آنووای دوطرفه جهت تجزیه و تحلیل داده­ها استفاده شد. یافته‌ها: تغییرات بیان ژن Wnt، GSK-3β و TSC2 در هیچ یک از گروه­ها در مقایسه با گروه کنترل معنا­دار نبود (P≥0.05). در گروه تعاملی تمرین مقاومتی و مکمل اسپیرولینا افزایش معنا­داری در میزان بیان ژن S6K درمقایسه با گروه کنترل مشاهده شد (017/0= P، 511/6F=). نتیجه‌گیری: با توجه  به عدم تاثیر مکمل اسپیرولینا بر سیگنالینگ Wnt به نظر می­رسد استفاده از این مکمل تاثیر منفی بر بافت کلیه نمی­گذارد، هر­چند با توجه به محدود بودن تحقیقات، بررسی­های بیشتر بر روی بافت کلیه بخصوص در نمونه­های بیمار توصیه می­شود.



عنوان مقاله [English]

The effect of eight weeks of resistance training and Spirulina platensis supplementation on the signaling pathway of Wnt-GSK3β-TSC2-S6K in the kidney tissue of male rats

نویسندگان [English]

  • Hamid Reza Sadeghipour 1
  • Fatemeh Raeisi 2
  • Abdossalehleh zar 3
1 Department of Sport Sciences, School of Literature and Humanities, Persian Gulf University, Boushehr, Iran.
2 Department of Sport Sciences, School of Literature and Humanities, Persian Gulf University, Boushehr, Iran
3 Associate professor, Department of Sport Science, School of Literature and Humanities, Persian Gulf University, Boushehr, Iran
چکیده [English]

Aim:      Wnt signaling is one of the most important signaling pathways involved in resistance training, which has a great molecular impact on the evolutionary path of kidney tissue. The aim of the present study was to investigate the effect of eight weeks of resistance training with spirulina supplementation on Wnt/GSK-3β/TSC2/S6K signaling pathway in the kidney tissue of male rats. Methods: In the experimental design, 32 young male rats at 3 months of age and an average weight of 150±20 grams were randomly divided into four groups: control, resistance exercise, spirulina supplement, and exercise+supplement. The resistance training groups performed the resistance exercise of climbing a ladder for eight weeks and 5 sessions per week (3 sets and 5 repetitions, 1-minute rest between repetitions and 2 minutes between sets). The intensity was 30% of the body weight in the first week and reached 100% in the final week. Spirulina in the amount of 200 mg/kg/day was added to the water of the supplementary groups. 24 hours after the last training session, kidney tissue was removed and the expression level of the dependent variables was measured using the REAL TIME-PCR method. Cross-sectional analysis of variance was used to analyze the data at a significant level of 0.05. Results: Changes in Wnt, GSK-3β and TSC2 gene expression were not significant in any of the groups compared to the control group (P≥0.05). In the interactive group of resistance exercise and Spirulina supplement, a significant increase in S6K gene expression was observed in comparison with the control group (P=0.017, F=6.511). Conclusion: Considering the lack of effect of Spirulina supplement on Wnt signaling, it seems that the use of spirulina does not have a negative effect on the kidney tissue, although due to the limited research, more investigations especially in the kidney patients are recommended.

کلیدواژه‌ها [English]

  • Resistance Training
  • Spirulina
  • Wnt Signaling
  1. Hawley, J.A., Molecular responses to strength and endurance training: are they incompatible? Applied physiology, nutrition, and metabolism, 2009. 34(3): p. 355-361.
  2. Spillane, M., N. Schwarz, and D.S. Willoughby, Upper-body resistance exercise augments vastus lateralis androgen receptor–DNA binding and canonical Wnt/β-catenin signaling compared to lower-body resistance exercise in resistance-trained men without an acute increase in serum testosterone. Steroids, 2015. 98: p. 63-71.
  3. Bashiri, J., A. NourAzar, and H. Purrazi, Effect of three months aerobic training on Wnt-signaling pathway in skeletal muscle of male rats. Razi Journal of Medical Sciences, 2017. 24(160): p. 7-16. [In Persian]
  4. 4. Dawson, K., M. Aflaki, and S. Nattel, Role of the Wnt‐Frizzled system in cardiac pathophysiology: a rapidly developing, poorly understood area with enormous potential. The Journal of physiology, 2013. 591(6): p. 1409-1432.
  5. 5. Karner, C.M., et al., Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis. Nature genetics, 2009. 41(7): p. 793-799.
  6. 6. Schunk, S.J., et al., WNT–β-catenin signalling—a versatile player in kidney injury and repair. Nature reviews Nephrology, 2021. 17(3): p. 172-184.
  7. 7. Edeling, M., et al., Developmental signalling pathways in renal fibrosis: the roles of Notch, Wnt and Hedgehog. Nature Reviews Nephrology, 2016. 12(7): p. 426-439.
  8. 8. Yang, Q., et al., Swimming training alleviated insulin resistance through Wnt3a/β-catenin signaling in type 2 diabetic rats. Iranian journal of basic medical sciences, 2017. 20(11): p. 1220.
  9. 9. Daneshmandi, H., A. Azamian Jazi, and B. Ghasemi, Effects of Eight Weeks of Moderate-Intensity Continuous and Resistance Training on The Glycogen Synthase Kinase-3 Beta Gene Expression, and Serum Glucose and Insulin Levels in Streptozotocin-Induced Diabetic Rats. Journal of Advanced Biomedical Sciences, 2020. 10(4): p. 2716-2727.
  10. 10. Doble, B.W. and J.R. Woodgett, GSK-3: tricks of the trade for a multi-tasking kinase. Journal of cell science, 2003. 116(7): 1175-1186.
  11. 11. Li, C., et al., The β isoform of GSK3 mediates podocyte autonomous injury in proteinuric glomerulopathy. The Journal of pathology, 2016. 239(1): p. 23-35.
  12. 12. Zhou, S., et al., Genetic and pharmacologic targeting of glycogen synthase kinase 3β reinforces the Nrf2 antioxidant defense against podocytopathy. Journal of the American Society of Nephrology: JASN, 2016. 27(8): p. 2289.
  13. 13. Liang, X., et al., Glycogen synthase kinase 3β hyperactivity in urinary exfoliated cells predicts progression of diabetic kidney disease. Kidney International, 2020. 97(1): p. 175-192.
  14. 14. Barone, S., et al., Kidney intercalated cells and the transcription factor FOXi1 drive cystogenesis in tuberous sclerosis complex. Proceedings of the National Academy of Sciences, 2021. 118(6): p. e2020190118.
  15. 15. Inoki, K., M.N. Corradetti, and K.-L. Guan, Dysregulation of the TSC-mTOR pathway in human disease. Nature genetics, 2005. 37(1): p. 19-24.
  16. 16. Androulakis-Korakakis, P., J.P. Fisher, and J. Steele, The minimum effective training dose required to increase 1RM strength in resistance-trained men: a systematic review and meta-analysis. Sports Medicine, 2020. 50(4): p. 751-765.
  17. 17. Ku, E., et al., Hypertension in CKD: core curriculum 2019. American Journal of Kidney Diseases, 2019. 74(1): p. 120-131.
  18. 18. Cockwell, P. and L.-A. Fisher, The global burden of chronic kidney disease. The Lancet, 2020. 395(10225): p. 662-664.
  19. 19. Silverwood, R.J., et al., Association between younger age when first overweight and increased risk for CKD. Journal of the American Society of Nephrology: JASN, 2013. 24(5): p. 813.
  20. 20. Gansevoort, R.T., et al., Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. The Lancet, 2013. 382(9889): p. 339-352.
  21. 21. Wang, Y., C.J. Zhou, and Y. Liu, Wnt signaling in kidney development and disease. Progress in molecular biology and translational science, 2018. 153: p. 181-207.
  22. 22. Tao, Y., et al., Rapamycin markedly slows disease progression in a rat model of polycystic kidney disease. Journal of the American Society of Nephrology, 2005. 16(1): p. 46-51.
  23. 23. Shillingford, J.M., et al., The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proceedings of the National Academy of Sciences, 2006. 103(14): p. 5466-5471.
  24. 24. Wahl, P.R., et al., Inhibition of mTOR with sirolimus slows disease progression in Han: SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrology Dialysis Transplantation, 2006. 21(3): p. 598-604.
  25. 25. Torres, V.E., et al., Prospects for mTOR inhibitor use in patients with polycystic kidney disease and hamartomatous diseases. Clinical journal of the American Society of Nephrology: CJASN, 2010. 5(7): p. 1312.
  26. 26. Takiar, V., et al., Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proceedings of the National Academy of Sciences, 2011. 108(6): p. 2462-2467.
  27. 27. Leonhard, W.N., et al., Salsalate, but not metformin or canagliflozin, slows kidney cyst growth in an adult-onset mouse model of polycystic kidney disease. EBioMedicine, 2019. 47: p. 436-445.
  28. 28. Lian, X., et al., The combination of metformin and 2‐deoxyglucose significantly inhibits cyst formation in miniature pigs with polycystic kidney disease. British Journal of Pharmacology, 2019. 176(5): p. 711-724.
  29. 29. Arazi, H., et al., Effects of different types of exercise on kidney diseases. Sports, 2022. 10(3): p. 42.
  30. 30. Böhm, J., et al., Acute effects of intradialytic aerobic exercise on solute removal, blood gases and oxidative stress in patients with chronic kidney disease. Brazilian Journal of Nephrology, 2017. 39: p. 172-180.
  31. 31. Fuhro, M.I., et al., Acute exercise during hemodialysis prevents the decrease in natural killer cells in patients with chronic kidney disease: a pilot study. International urology and nephrology, 2018. 50: p. 527-534.
  32. 32. Kirkman, D.L., et al., Cardiopulmonary exercise testing reveals subclinical abnormalities in chronic kidney disease. European Journal of Preventive Cardiology, 2018. 25(16): p. 1717-1724.
  33. 33. Stringuetta Belik, F., et al., Influence of intradialytic aerobic training in cerebral blood flow and cognitive function in patients with chronic kidney disease: a pilot randomized controlled trial. Nephron, 2018. 140(1): p. 9-17.
  34. 34. Huang, M., et al., The effect of intradialytic combined exercise on hemodialysis efficiency in end-stage renal disease patients: a randomized-controlled trial. International Urology and Nephrology, 2020. 52: p. 969-976.
  35. 35. Jankowski, J., et al., Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic options. Circulation, 2021. 143(11): p. 1157-1172.
  36. 36. Watson, E.L., et al., Progressive resistance exercise training in CKD: a feasibility study. American Journal of Kidney Diseases, 2015. 66(2): p. 249-257.
  37. 37. Lupatini, A.L., et al., Potential application of microalga Spirulina platensis as a protein source. Journal of the Science of Food and Agriculture, 2017. 97(3): p. 724-732.
  38. 38. Zeinalian, R., et al., The effects of Spirulina Platensis on anthropometric indices, appetite, lipid profile and serum vascular endothelial growth factor (VEGF) in obese individuals: a randomized double blinded placebo controlled trial. BMC complementary and alternative medicine, 2017. 17: p. 1-8.
  39. 39. Hernandez Lepe, M.A., Effect of exercise and/or spirulina maxima on body composition in overweight/obese humans. Producto de investigación ICB, 2018.
  40. 40. Gao, H., et al., Protective Effect of Lycium ruthenicum Polyphenols on Oxidative Stress against Acrylamide Induced Liver Injury in Rats. Molecules, 2022. 27(13): p. 4100.
  41. 41. Sandhu, J., B. Dheera, and S. Shweta, Efficacy of spirulina supplementation on isometric strength and isometric endurance of quadriceps in trained and untrained individuals–a comparative study. Ibnosina Journal of Medicine and Biomedical Sciences, 2010. 2(02): p. 79-86.
  42. 42. Chen, Y., et al., In vivo antifatigue activity of spirulina peptides achieved by their antioxidant activity and by acting on fat metabolism pathway in mice. Natural Product Communications, 2020. 15(8): p. 1934578X20946233.
  43. 43. Liping, L., et al., Spirulina platensis extract supplementation attenuates oxidative stress in acute exhaustive exercise: a pilot study. International Journal of Physical Sciences, 2011. 6(12): p. 2901-6.
  44. 44. Ghodsbin, S., S. Farsi, and S.A. Hosseini, Correlation between CRP and IL-6 serum levels after induction of diabetes and eight weeks resistance training in rats. Report of Health Care, 2017. 3(4): 1-9.
  45. 45. Dehghan, F., et al., Saffron with resistance exercise improves diabetic parameters through the GLUT4/AMPK pathway in-vitro and in-vivo. Scientific reports, 2016. 6(1): p. 25139.
  46. 46. Zar, A., & Ahmadi, F., Evaluation of CITED4 Gene Expression in The Cardiac Muscle of Male Rats as a Result of Resistance Exercise and Spirulina Supplement. Jorjani Biomedicine Journa, 2021. 9(2): p. 36-44. [In Persian]
  47. 47. Soltanmohammadi, F., M. Mohsenzadeh, and F. Feizollahi, THE EFFECT OF 8 WEEKS OF HIIT TRAINING AND SUPPLEMENTATION OF BLACK GRAPE SEED EXTRACT ON WNT AND Β-CATENIN GENE EXPRESSION IN PANCREATIC TISSUE IN MALE RATS WITH TYPE 2 DIABETES. Iranian Journal of Diabetes and Metabolism, 2020. 19(2): p. 61-70. [In Persian]
  48. 48. Leal, M.L., et al., Effect of different resistance-training regimens on the WNT-signaling pathway. European journal of applied physiology, 2011. 111: p. 2535-2545.
  49. 49. Asgharpour-arshad, M., H. POURRAZI, and R. Bakhshi, The effect of high intensity interval training (HIIT) on cardiac hypertrophy: the role of Wnt/β-catenin signaling pathway. Metabolism and Exercise, 2021. 11(2): p. 43-55. [In Persian]
  50. 50. Vissing, K., et al., Differentiated mTOR but not AMPK signaling after strength vs endurance exercise in training‐accustomed individuals. Scandinavian journal of medicine & science in sports, 2013. 23(3): p. 355-366.
  51. 51. Kim, D.-Y., et al., Treadmill exercise decreases incidence of Alzheimer’s disease by suppressing glycogen synthase kinase-3β expression in streptozotocin-induced diabetic rats. Journal of exercise rehabilitation, 2015. 11(2): p. 87.
  52. 52. Ebrahimi M, A.H., Rezaii R, Farzanegi P., The Effect of Two Types of Exercise (Continuous and Intermittent) on the Expression of PP2Ac and NF-κB Genes in the Heart Tissue of Diabetic Rat. RJMS, 2023. 30(4): p. 14-2 [In Persian]
  53. 53. Fujimaki, S., et al., Wnt protein-mediated satellite cell conversion in adult and aged mice following voluntary wheel running. Journal of biological chemistry, 2014. 289(11): p. 7399-7412.
  54. 54. Mousavi Mozafar, S.M., M. Nourshahi, and A. Akbarnejad, Muscle Murf1 and P70S6K Before and After 6 Weeks of Resistance Training and HMB Supplementation in Inactive Men. Sport Physiology, 2020. 12(45): p. 79-94. [In Persian]
  55. 55. Sunami, T., et al., Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop phosphorylation. Journal of Biological Chemistry, 2010. 285(7): p. 4587-4594.
  56. 56. Basualto-Alarcón, C., et al., Testosterone signals through mTOR and androgen receptor to induce muscle hypertrophy. Medicine and science in sports and exercise, 2013. 45(9): 1712-1720.
  57. 57. Krug, A.L., et al., High‐intensity resistance training attenuates dexamethasone‐induced muscle atrophy. Muscle & nerve, 2016. 53(5): p. 779-788.
  58. 58. Aghaei Bahman Beglou, N., Shadmehri, S., Jahani Golbar, S., & Sharafati Moghadam, M, The effect of four weeks high-intensity interval training (HIIT) on the content of AKT1, mTOR, P70S6K1, 4EBP1 proteins in the Left ventricular muscle tissue of the heart obese rats with type 2 diabetic. ournal of Sport and Exercise Physiology, 2021. 14(1): 85-94. [In Persian]
  59. 59. Sherafati Moghadam, M., Salesi, M., Daryanoosh, F., Hemati Nafar, M., & Fallahi, A, The effect of 4 weeks of high intensity interval training on the content of AKT1, mTOR, P70S6K1 and 4E-BP1 in soleus skeletal muscle of rats with type 2 diabetes: An experimental study. Journal of Rafsanjan University of Medical Sciences, 2018. 17(9): p. 843-859. [In Persian]
  60. 60. Shabani, M., Moghadam, M. S., & Moghaddami, K, Effect of 8 Weeks of Endurance Training on S6K1 and 4EBP1 Proteins Content in the Left Ventricle of the Heart of Diabetic Rats Induced by Streptozotocin and Nicotinamide. Journal of Shahid Sadoughi University of Medical Sciences, 2021. [In Persian]
  61. 61. Lin, X., et al., Role of the Wnt/β-catenin signaling pathway in inducing apoptosis and renal fibrosis in 5/6-nephrectomized rats. Molecular medicine reports, 2017. 15(6): p. 3575-3582.