فیزیولوژی ورزشی

فیزیولوژی ورزشی

تاثیر هشت هفته تمرین ترکیبی بر بیان miR-146a، miR-21 و TLR-2 خون در زنان مبتلا به مولتیپل اسکلروزیس عودکننده- فروکش کننده

نوع مقاله : مقاله پژوهشی

نویسندگان
اکبر اعظمیان جزی 1
محمد شاه وردی شهرکی 2
محمد ربیعی 3
1 دانشیار، گروه علوم ورزشی، گروه علوم ورزشی، دانشکده ادبیات و علوم انسانی، دانشگاه شهرکرد، شهرکرد، ایران
2 دانشجوی کارشناسی ارشد فیزیولوژی ورزشی، گروه علوم ورزشی، دانشکده ادبیات و علوم انسانی، دانشگاه شهرکرد، شهرکرد، ایران
3 استادیار، گروه علوم ورزشی، دانشکده ادبیات و علوم انسانی، دانشگاه شهرکرد، شهرکرد، ایران
10.22089/spj.2025.16955.2320
چکیده
هدف: miR-146a، miR-21 و TLR-2 در فرایندهای ضد التهابی، میلین‌سازی مجدد و تنظیم پاسخ­های خود­ایمنی نقش دارند که ممکن است تحت تأثیر تمرینات ورزشی قرار گیرند. بنابراین، این مطالعه با هدف بررسی تاثیر هشت هفته تمرین ترکیبی بر بیان miR-146a، miR-21 و TLR-2 در زنان مبتلا به بیماری مولتیپل اسکلروزیس عودکننده- فروکش کننده (RRMS) انجام شد.
مواد و روش ها: بیست و سه زن (سن: 3/5±1/33 سال، وزن: 9/8±1/64 کیلوگرم و BMI: 4/9±3/33 کیلوگرم بر متر مربع) مبتلا به RRMS به طور تصادفی در دو گروه تمرین و کنترل قرار گرفتند. آزمودنی‌های گروه تمرین به مدت هشت هفته در تمرین ترکیبی تحت نظارت، شامل سه جلسه تمرین هوازی و یک جلسه تمرین مقاومتی شرکت کردند. بیان miR-146a، miR-21 و TLR-2 در خون قبل و بعد از هشت هفته تمرین ترکیبی با استفاده از تکنیک RT-PCR اندازه­گیری شد. داده­ها با آزمون آنوآ دو طرفه با اندازه­گیری­های مکرر و در سطح معناداری کم­تر از 05/0 آنالیز شد.
یافته ها: تحلیل داده­‌ها نشان داد که بیان نسبی miR-146a در زنان مبتلا به RRMS پس از هشت هفته تمرین ترکیبی در گروه تمرین نسبت به گروه کنترل به طور معناداری کمتر کاهش یافت (001/0P=) و بر عکس، بیان نسبی miR-21 و TLR-2 در گروه تمرین نسبت به گروه کنترل به طور معناداری کمتر افزایش یافت (001/0P=).
نتیجه گیری: تمرین ترکیبی ممکن است با تاثیر مطلوب بر miR-146a، miR-21 و TLR-2 نقش موثری در پیش­برد فرایند­های ضد التهابی، میلین‌سازی مجدد و تنظیم پاسخ­های خود­ایمنی در بیماری RRMS داشته باشد و در نتیجه، این بیماری را بهبود بخشیده و احتمال عود آن را کاهش دهد. بنابراین، استفاده از تمرین ترکیبی این تحقیق برای زنان مبتلا به RRMS توصیه می­شود.
کلیدواژه‌ها
مولتیپل اسکلروزیس
تمرین ترکیبی
miR-146a
miR-21
TLR-2
موضوعات
1.   Barry A, Cronin O, Ryan AM, Sweeney B, Yap SM, O'Toole O, et al. Impact of Exercise on Innate Immunity in Multiple Sclerosis Progression and Symptomatology. Front Physiol. 2016;7:194. https://doi.org/10.3389/fphys.2016.00194
2.   Zameer U, Tariq A, Asif F, Kamran A. Empowering Minds and Bodies: The Impact of Exercise on Multiple Sclerosis and Cognitive Health. Ann Neurosci. 2024;31(2):121-3. https://doi.org/10.1177/09727531241227674
3.   Petropoulos IN, John K, Al-Shibani F, Ponirakis G, Khan A, Gad H, et al. Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study. Ther Adv Neurol Disord. 2023;16:17562864231204974. https://doi.org/10.1177/17562864231204974
4.   Baggish AL, Hale A, Weiner RB, Lewis GD, Systrom D, Wang F, et al. Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training. J Physiol. 2011;589(Pt 16):3983-94. https://doi.org/10.1113/jphysiol.2011.213363
5.   Ma X, Zhou J, Zhong Y, Jiang L, Mu P, Li Y, et al. Expression, regulation and function of microRNAs in multiple sclerosis. Int J Med Sci. 2014;11(8):810-8. https://doi.org/10.7150/ijms.8647
6.   Muñoz-San Martín M, Reverter G, Robles-Cedeño R, Buxò M, Ortega FJ, Gómez I, et al. Analysis of miRNA signatures in CSF identifies upregulation of miR-21 and miR-146a/b in patients with multiple sclerosis and active lesions. J Neuroinflammation. 2019;16(1):220. https://doi.org/10.1186/s12974-019-1590-5
7.   Oliveira-Nascimento L, Massari P, Wetzler LM. The Role of TLR2 in Infection and Immunity. Front Immunol. 2012;3:79. https://doi.org/10.3389/fimmu.2012.00079
8.   Perdaens O, Bottemanne P, van Pesch V. MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell line. Front Cell Neurosci. 2024;18:1336439. https://doi.org/10.3389/fncel.2024.1336439
9.   Geiger L, Orsi G, Cseh T, Gombos K, Illés Z, Czéh B. Circulating microRNAs correlate with structural and functional MRI parameters in patients with multiple sclerosis. Front Mol Neurosci. 2023;16:1173212. https://doi.org/10.3389/fnmol.2023.1173212
10. Alevizos I, Illei GG. MicroRNAs in Sjogren's syndrome as a prototypic autoimmune disease. Autoimmunity reviews. 2010;9(9):618-21. https://doi.org/10.1016/j.autrev.2010.05.009
11. Duffy CP, McCoy CE. The role of MicroRNAs in repair processes in multiple sclerosis. Cells. 2020;9(7):1711. https://doi.org/10.3390/cells9071711
12. Junker A, Krumbholz M, Eisele S, Mohan H, Augstein F, Bittner R, et al. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain. 2009;132(Pt 12):3342-52. https://doi.org/10.1093/brain/awp300
13. Saba R, Gushue S, Huzarewich RL, Manguiat K, Medina S, Robertson C, et al. MicroRNA 146a (miR-146a) is over-expressed during prion disease and modulates the innate immune response and the microglial activation state. PLoS One. 2012;7(2):e30832. https://doi.org/10.1371/journal.pone.0030832
14. Moraghebi M, Negahi AA, Bazireh H, Abbasi H, Ahmadi M, Sarikhani Z, et al. The Analysis of SNPs' Function in miR-21 and miR146a/b in Multiple Sclerosis and Active Lesions: An In Silico Study. Bioinform Biol Insights. 2022;16:11779322221116322. https://doi.org/10.1177/11779322221116322
15. Garo LP, Murugaiyan G. Contribution of MicroRNAs to autoimmune diseases. Cell Mol Life Sci. 2016;73(10):2041-51. https://doi.org/10.1007/s00018-016-2167-4
16. Quinn SR, O'Neill LA. A trio of microRNAs that control Toll-like receptor signalling. International immunology. 2011;23(7):421-5. https://doi.org/10.1093/intimm/dxr034
17. Fan W, Liang C, Ou M, Zou T, Sun F, Zhou H, et al. MicroRNA-146a Is a Wide-Reaching Neuroinflammatory Regulator and Potential Treatment Target in Neurological Diseases. Front Mol Neurosci. 2020;13:90. https://doi.org/10.3389/fnmol.2020.00090
18. Wang J, Yu JT, Tan L, Tian Y, Ma J, Tan CC, et al. Genome-wide circulating microRNA expression profiling indicates biomarkers for epilepsy. Sci Rep. 2015;5:9522. https://doi.org/10.1038/srep09522
19. Müller M, Kuiperij HB, Versleijen AA, Chiasserini D, Farotti L, Baschieri F, et al. Validation of microRNAs in Cerebrospinal Fluid as Biomarkers for Different Forms of Dementia in a Multicenter Study. J Alzheimers Dis. 2016;52(4):1321-33. https://doi.org/10.3233/jad-160038
20. Ma SQ, Xu XX, He ZZ, Li XH, Luo JM. Dynamic changes in peripheral blood-targeted miRNA expression profiles in patients with severe traumatic brain injury at high altitude. Mil Med Res. 2019;6(1):12. https://doi.org/10.1186/s40779-019-0203-z
21. Ahmed Ali M, Gamil Shaker O, Mohamed Eid H, Elsayed Mahmoud E, Mahmoud Ezzat E, Nady Gaber S. Relationship between miR-155 and miR-146a polymorphisms and susceptibility to multiple sclerosis in an Egyptian cohort. Biomed Rep. 2020;12(5):276-84. https://doi.org/10.3892/br.2020.1286
22. Zamani A, Dehghan Manshadi M, Akouchekian M, Salahshouri Far I. The Association of miRNA-146a Gene Variation and Multiple Sclerosis in The Iranian Population. Med J Islam Repub Iran. 2024;38:1. https://doi.org/10.47176/mjiri.38.1
23. Quintana E, Ortega FJ, Robles-Cedeño R, Villar ML, Buxó M, Mercader JM, et al. miRNAs in cerebrospinal fluid identify patients with MS and specifically those with lipid-specific oligoclonal IgM bands. Mult Scler. 2017;23(13):1716-26. https://doi.org/10.1177/1352458516684213
24. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006;103(33):12481-6. https://doi.org/10.1073/pnas.0605298103
25. Sonkoly E, Ståhle M, Pivarcsi A. MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation. Semin Cancer Biol. 2008;18(2):131-40. https://doi.org/10.1016/j.semcancer.2008.01.005
26. Li YY, Cui JG, Dua P, Pogue AI, Bhattacharjee S, Lukiw WJ. Differential expression of miRNA-146a-regulated inflammatory genes in human primary neural, astroglial and microglial cells. Neurosci Lett. 2011;499(2):109-13. https://doi.org/10.1016/j.neulet.2011.05.044
27. García-Jacobo RE, Uresti-Rivera EE, Portales-Pérez DP, González-Amaro R, Lara-Ramírez EE, Enciso-Moreno JA, et al. Circulating miR-146a, miR-34a and miR-375 in type 2 diabetes patients, pre-diabetic and normal-glycaemic individuals in relation to β-cell function, insulin resistance and metabolic parameters. Clin Exp Pharmacol Physiol. 2019;46(12):1092-100. https://doi.org/10.1111/1440-1681.13147
28. Martin NA, Molnar V, Szilagyi GT, Elkjaer ML, Nawrocki A, Okarmus J, et al. Experimental Demyelination and Axonal Loss Are Reduced in MicroRNA-146a Deficient Mice. Front Immunol. 2018;9:490. https://doi.org/10.3389/fimmu.2018.00490
29. Giuliani A, Lattanzi S, Ramini D, Graciotti L, Danni MC, Procopio AD, et al. Potential prognostic value of circulating inflamma-miR-146a-5p and miR-125a-5p in relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2021;54:103126. https://doi.org/10.1016/j.msard.2021.103126
30. Loboda A, Sobczak M, Jozkowicz A, Dulak J. TGF-β1/Smads and miR-21 in Renal Fibrosis and Inflammation. Mediators Inflamm. 2016;2016:8319283. https://doi.org/10.1155/2016/8319283
31. Manian M, Sohrabi E, Eskandari N, Assarehzadegan MA, Ferns GA, Nourbakhsh M, et al. An Integrated Bioinformatics Analysis of the Potential Regulatory Effects of miR-21 on T-cell Related Target Genes in Multiple Sclerosis. Avicenna J Med Biotechnol. 2021;13(3):149-65. https://doi.org/10.18502/ajmb.v13i3.6364
32. Ntranos A, Ntranos V, Bonnefil V, Liu J, Kim-Schulze S, He Y, et al. Fumarates target the metabolic-epigenetic interplay of brain-homing T cells in multiple sclerosis. Brain. 2019;142(3):647-61. https://doi.org/10.1093/brain/awy344
33. Fenoglio C, Cantoni C, De Riz M, Ridolfi E, Cortini F, Serpente M, et al. Expression and genetic analysis of miRNAs involved in CD4+ cell activation in patients with multiple sclerosis. Neurosci Lett. 2011;504(1):9-12. https://doi.org/10.1016/j.neulet.2011.08.021
34. Hernández-Pedro NY, Espinosa-Ramirez G, de la Cruz VP, Pineda B, Sotelo J. Initial immunopathogenesis of multiple sclerosis: innate immune response. Clin Dev Immunol. 2013;2013:413465. https://doi.org/10.1155/2013/413465
35. Colleselli K, Stierschneider A, Wiesner C. An Update on Toll-like Receptor 2, Its Function and Dimerization in Pro- and Anti-Inflammatory Processes. Int J Mol Sci. 2023;24(15). https://doi.org/10.3390/ijms241512464
36. Bsibsi M, Nomden A, van Noort JM, Baron W. Toll-like receptors 2 and 3 agonists differentially affect oligodendrocyte survival, differentiation, and myelin membrane formation. J Neurosci Res. 2012;90(2):388-98. https://doi.org/10.1002/jnr.22767
37. Hayward JH, Lee SJ. A Decade of Research on TLR2 Discovering Its Pivotal Role in Glial Activation and Neuroinflammation in Neurodegenerative Diseases. Exp Neurobiol. 2014;23(2):138-47. https://doi.org/10.5607/en.2014.23.2.138
38. Nyirenda MH, Morandi E, Vinkemeier U, Constantin-Teodosiu D, Drinkwater S, Mee M, et al. TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis. J Immunol. 2015;194(12):5761-74. https://doi.org/10.4049/jimmunol.1400472
39. Sloane JA, Batt C, Ma Y, Harris ZM, Trapp B, Vartanian T. Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2. Proc Natl Acad Sci U S A. 2010;107(25):11555-60. https://doi.org/10.1073/pnas.1006496107
40. Jafarzadeh A, Nemati M, Khorramdelazad H, Mirshafiey A. The Toll-like Receptor 2 (TLR2)-related Immunopathological Responses in the Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. Iran J Allergy Asthma Immunol. 2019;18(3):230-50. https://doi.org/10.18502/ijaai.v18i3.1117
41. Deckx N, Wens I, Nuyts AH, Hens N, De Winter BY, Koppen G, et al. 12 Weeks of Combined Endurance and Resistance Training Reduces Innate Markers of Inflammation in a Randomized Controlled Clinical Trial in Patients with Multiple Sclerosis. Mediators Inflamm. 2016;2016:6789276. https://doi.org/10.1155/2016/6789276
42. Golzari Z, Shabkhiz F, Soudi S, Kordi MR, Hashemi SM. Combined exercise training reduces IFN-γ and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis. Int Immunopharmacol. 2010;10(11):1415-9. https://doi.org/10.1016/j.intimp.2010.08.008
43. Guillamó E, Cobo-Calvo Á, Oviedo GR, Travier N, Álamo J, Niño-Mendez OA, et al. Feasibility and Effects of Structured Physical Exercise Interventions in Adults with Relapsing-Remitting Multiple Sclerosis: A Pilot Study. J Sports Sci Med. 2018;17(3):426-36. Available at: https://pubmed.ncbi.nlm.nih.gov/30116116/.
44. Motl RW, Sandroff BM, Benedict RH. Cognitive dysfunction and multiple sclerosis: developing a rationale for considering the efficacy of exercise training. Mult Scler. 2011;17(9):1034-40. https://doi.org/10.1177/1352458511409612
45. Sangelaji B, Kordi M, Banihashemi F, Nabavi SM, Khodadadeh S, Dastoorpoor M. A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial. Iran J Neurol. 2016;15(3):111-20. Available at: https://pubmed.ncbi.nlm.nih.gov/27648171/.
46. Hoekstra M, van der Lans CA, Halvorsen B, Gullestad L, Kuiper J, Aukrust P, et al. The peripheral blood mononuclear cell microRNA signature of coronary artery disease. Biochemical and biophysical research communications. 2010;394(3):792-7. https://doi.org/10.1016/j.bbrc.2010.03.075
47. Radom-Aizik S, Zaldivar FP, Jr., Haddad F, Cooper DM. Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease. Brain, behavior, and immunity. 2014;39:121-9. https://doi.org/10.1016/j.bbi.2014.01.003
48. Da Silva FC, Rode MP, Vietta GG, Iop RDR, Creczynski-Pasa TB, Martin AS, et al. Expression levels of specific microRNAs are increased after exercise and are associated with cognitive improvement in Parkinson's disease. Mol Med Rep. 2021;24(2). https://doi.org/10.3892/mmr.2021.12257
49. Rafiei MM, Soltani R, Kordi MR, Nouri R, Gaeini AA. Gene expression of angiogenesis and apoptotic factors in female BALB/c mice with breast cancer after eight weeks of aerobic training. Iran J Basic Med Sci. 2021;24(9):1196-202. https://doi.org/10.22038/ijbms.2021.55582.12427
50. Yousefi Saqqezi S, Azamian Jazi A, Hemmati R, Jivad N. Combined Training Improves the Expression Profile of Inflammation-associated Antimicrobial Peptides, MicroRNAs, and TLR-4 in Patients with Multiple Sclerosis. Iran J Allergy Asthma Immunol. 2021;20(4):441-52. Available at: https://pubmed.ncbi.nlm.nih.gov/34418898/.
51. Katz Sand I. Classification, diagnosis, and differential diagnosis of multiple sclerosis. Curr Opin Neurol. 2015;28(3):193-205. https://doi.org/10.1097/wco.0000000000000206
52. Witvrouwen I, Gevaert AB, Possemiers N, Ectors B, Stoop T, Goovaerts I, et al. Plasma-Derived microRNAs Are Influenced by Acute and Chronic Exercise in Patients With Heart Failure With Reduced Ejection Fraction. Front Physiol. 2021;12:736494. https://doi.org/10.3389/fphys.2021.736494
53. Zhang J, Zhang ZG, Lu M, Wang X, Shang X, Elias SB, et al. MiR-146a promotes remyelination in a cuprizone model of demyelinating injury. Neuroscience. 2017;348:252-63. https://doi.org/0.1016/j.neuroscience.2017.02.029
54. Zhang J, Zhang ZG, Lu M, Zhang Y, Shang X, Chopp M. MiR-146a promotes oligodendrocyte progenitor cell differentiation and enhances remyelination in a model of experimental autoimmune encephalomyelitis. Neurobiol Dis. 2019;125:154-62. https://doi.org/10.1016/j.nbd.2019.01.019
55. Aslani M, Mortazavi-Jahromi SS, Mirshafiey A. Efficient roles of miR-146a in cellular and molecular mechanisms of neuroinflammatory disorders: An effectual review in neuroimmunology. Immunology Letters. 2021;238:1-20. https://doi.org/10.1016/j.imlet.2021.07.004
56. Nielsen S, Åkerström T, Rinnov A, Yfanti C, Scheele C, Pedersen BK, et al. The miRNA plasma signature in response to acute aerobic exercise and endurance training. PLoS One. 2014;9(2):e87308. https://doi.org/10.1371/journal.pone.0087308
57. Delphan M, Agha Alinejad H, Delfan M, Dehghan S. Intratumoral Effects of Continuous Endurance Training and High Intensity Interval Training on Genes Expression of miR-21 and bcl-2 in Breast Cancer Bearing Female mice. Iranian Journal of Breast Diseases. 2017;10(2):49-57. Available at: https://ijbd.ir/article-1-629-fa.html. [In Persian].
58. Soltani R, Kordi MR, Gaeini AA, Nuri R. The effects of 8 weeks aerobic training on HIF-1α, miR-21 and VEGF gene expression in female Balb/c with breast cancer. scientific magazine yafte. 2019;21(1):63-74. Available at: https://yafte.lums.ac.ir/article-1-2760-en.html. [In Persian].
59. Bai X, Bian Z. MicroRNA-21 Is a Versatile Regulator and Potential Treatment Target in Central Nervous System Disorders. Front Mol Neurosci. 2022;15:842288. https://doi.org/10.3389/fnmol.2022.842288
60. Wang L, Liang Y. MicroRNAs as T Lymphocyte Regulators in Multiple Sclerosis. Front Mol Neurosci. 2022;15:865529. https://doi.org/10.3389/fnmol.2022.865529
61. Najafi N, Seifi-Skishahr F, Afroundeh R. The Effect of twelve weeks Interval Resistance Training with different intensity on TLR2,4 Dectin-1 in obese men. Metabolism and Exercise. 2022;12(1):205-20. https://doi.org/10.22124/jme.2023.23629.237. [In Persian].
62. Stewart LK, Flynn MG, Campbell WW, Craig BA, Robinson JP, McFarlin BK, et al. Influence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4. Brain, behavior, and immunity. 2005;19(5):389-97. https://doi.org/10.1016/j.bbi.2005.04.003
63. Zong B, Yu F, Zhang X, Zhao W, Li S, Li L. Mechanisms underlying the beneficial effects of physical exercise on multiple sclerosis: focus on immune cells. Front Immunol. 2023;14:1260663. https://doi.org/10.3389/fimmu.2023.1260663
64. Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 2015;21(7):677-87. https://doi.org/10.1038/nm.3893
65. Liu HW, Chang SJ. Moderate Exercise Suppresses NF-κB Signaling and Activates the SIRT1-AMPK-PGC1α Axis to Attenuate Muscle Loss in Diabetic db/db Mice. Front Physiol. 2018;9:636. https://doi.org/10.3389/fphys.2018.00636
66. Nahid MA, Satoh M, Chan EK. Mechanistic role of microRNA-146a in endotoxin-induced differential cross-regulation of TLR signaling. J Immunol. 2011;186(3):1723-34. https://doi.org/10.4049/jimmunol.1002311
67. Saba R, Sorensen DL, Booth SA. MicroRNA-146a: A Dominant, Negative Regulator of the Innate Immune Response. Front Immunol. 2014;5:578. https://doi.org/10.3389/fimmu.2014.00578
68. Meisgen F, Xu Landén N, Wang A, Réthi B, Bouez C, Zuccolo M, et al. MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes. J Invest Dermatol. 2014;134(7):1931-40. https://doi.org/10.1038/jid.2014.89
69. Bayraktar R, Bertilaccio MTS, Calin GA. The interaction between two worlds: MicroRNAs and toll-like receptors. Front Immunol. 2019;10:1053. https://doi.org/10.3389/fimmu.2019.01053
 
end
فیزیولوژی ورزشی
دوره 17، شماره 67
پاییز 1404
صفحه 17-46

  • تاریخ دریافت 11 تیر 1403
  • تاریخ بازنگری 10 خرداد 1404
  • تاریخ پذیرش 19 خرداد 1404