骨骼肌细胞凋亡的调控机制： 体育锻炼与天然活性化合物的作用

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细胞凋亡在维持骨骼肌组织稳态中发挥着关键作用。然而，在肥胖、2型糖尿病及年龄相关变化的背景下，其调控机制可能发生紊乱，导致肌肉加速退化、功能减退以及代谢障碍的发展。本文综述了骨骼肌细胞凋亡的调控机制，重点探讨了两大关键因素——体育锻炼与天然生物活性化合物的影响。科学研究证实，体育锻炼以及白藜芦醇、姜黄素、槲皮素等天然活性化合物具有显著的抗细胞凋亡作用，其机制包括减轻氧化应激、改善线粒体功能和调控Bcl-2及AMPK/SIRT1信号通路。二者联用具有协同作用，是预防和治疗肌少症、肥胖及其相关代谢性疾病的有前景策略。尽管实验研究结果显示出良好前景，仍需进一步开展临床试验，以优化体育活动方案并筛选出最优天然活性化合物组合，以期预防肌肉萎缩并改善患者的代谢状况。

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作者简介

Alina B. Marzhanova

Rostov State Medical University

编辑信件的主要联系方式.
Email: murkudda@mail.ru
ORCID iD: 0009-0006-5910-8739
俄罗斯联邦, Rostov-On-Don

Elizaveta K. Lapitskaya

Orenburg State Medical University

Email: liza.lapickaya@mail.ru
ORCID iD: 0009-0004-4535-4184
俄罗斯联邦, Orenburg

Aminat Sungurova

The First Sechenov Moscow State Medical University

Email: Aammiiinnnkkaa@mail.ru
ORCID iD: 0009-0005-8692-4777
俄罗斯联邦, Moscow

Marina A. Marzoeva

Pirogov Russian National Research Medical University

Email: marzoeva_m99@mail.ru
ORCID iD: 0000-0003-4391-0218
SPIN 代码: 2365-8824
俄罗斯联邦, Moscow

Regina I. Balagutdinova

Bashkir State Medical University

Email: regina.balagutdinova@inbox.ru
ORCID iD: 0009-0008-3398-2721
俄罗斯联邦, Ufa

Aigul R. Nasyrova

Bashkir State Medical University

Email: Shoning228@mail.ru
ORCID iD: 0009-0005-2164-044X
俄罗斯联邦, Ufa

Taisa A. Khasukhanova

Pirogov Russian National Research Medical University

Email: borealis.k@mail.ru
ORCID iD: 0009-0001-2124-6064
俄罗斯联邦, Moscow

Azat I. Kutlubaev

Orenburg State Medical University

Email: kutlubaev_2015@mail.ru
ORCID iD: 0009-0009-6636-533X
俄罗斯联邦, Orenburg

Kristina S. Ivanova

The First Sechenov Moscow State Medical University

Email: christina_ivanova01@mail.ru
ORCID iD: 0009-0009-6699-3432
俄罗斯联邦, Moscow

Diana S. Ispieva

Pirogov Russian National Research Medical University

Email: ispievadiana@yandex.ru
ORCID iD: 0009-0005-4863-1957
俄罗斯联邦, Moscow

Anastasia S. Nalivaiko

Vernadsky Crimean Federal University

Email: Anastasia.Nalivaiko01@mail.ru
ORCID iD: 0009-0009-2220-5174
俄罗斯联邦, Simferopol

Eduard A. Sukasyan

Vernadsky Crimean Federal University

Email: sukasyan1999@bk.ru
ORCID iD: 0009-0007-0054-5747
SPIN 代码: 7667-1390
俄罗斯联邦, Simferopol

Polina A. Bulgakova

Vernadsky Crimean Federal University

Email: pbulgakova75@gmail.com
ORCID iD: 0009-0002-6314-6093
俄罗斯联邦, Simferopol

Elizaveta A. Fedotova

Volgograd State Medical University

Email: crosszery2610200143@mail.ru
ORCID iD: 0009-0009-8382-6345
俄罗斯联邦, Volgograd

Danila D. Sattarov

Bashkir State Medical University

Email: danila.sattarov@gmail.com
ORCID iD: 0009-0001-4784-5997
俄罗斯联邦, Ufa

参考

  1. Dedov II, Shestakova MV, Melnichenko GA, et al. Interdisciplinary clinical practice guidelines “management of obesity and its comorbidities”. Obesity and metabolism. 2021;18(1):5–99. doi: 10.14341/omet12714 EDN: AHSBSE
  2. Dalili D, Bazzocchi A, Dalili DE, et al. The role of body composition assessment in obesity and eating disorders. Eur J Radiol. 2020;131:109227. doi: 10.1016/j.ejrad.2020.109227
  3. Lingvay I, Cohen RV, Roux CWL, Sumithran P. Obesity in adults. Lancet. 2024;404(10456):972–987. doi: 10.1016/S0140-6736(24)01210-8
  4. Bondareva EA, Troshina EA. Obesity. Reasons, features and prospects. Obesity and metabolism. 2024;21(2):174–187. doi: 10.14341/omet13055 EDN: BRPHRR
  5. Razina AO, Achkasov EE, Runenko SD. Obesity: the modern approach to the problem. Obesity and metabolism. 2016;13(1):3–8. doi: 10.14341/omet201613-8
  6. Anekwe CV, Jarrell AR, Townsend MJ, Gaudier GI, Hiserodt JM, Stanford FC. Socioeconomics of Obesity. Curr Obes Rep. 2020;9(3):272–279. doi: 10.1007/s13679-020-00398-7
  7. Mustafina SV, Vinter DA, Alferova VI. Influence of obesity on the formation and development of cancer. Obesity and metabolism. 2024;21(2):205–214. doi: 10.14341/omet13025 EDN: HGLCXT
  8. Anekwe CV, Jarrell AR, Townsend MJ, et al. Socioeconomics of Obesity. Curr Obes Rep. 2020;9(3):272–279. doi: 10.1007/s13679-020-00398-7
  9. Keane KN, Cruzat VF, Carlessi R, et al. Molecular Events Linking Oxidative Stress and Inflammation to Insulin Resistance and β-Cell Dysfunction. Oxid Med Cell Longev. 2015;2015:181643. doi: 10.1155/2015/181643
  10. Röszer T. Adipose Tissue Immunometabolism and Apoptotic Cell Clearance. Cells. 2021;10(9):2288. doi: 10.3390/cells10092288
  11. Wondmkun YT. Obesity, Insulin Resistance, and Type 2 Diabetes: Associations and Therapeutic Implications. Diabetes Metab Syndr Obes. 2020;13:3611–3616. doi: 10.2147/DMSO.S275898
  12. Kyazimova ND, Kornyakova VV. Influence of polyphenolic compounds on human health and the course of a number of diseases. Scientific Bulletin of the Omsk State Medical University. 2024;4(1):87–91. doi: 10.61634/2782-3024-2024-13-87-91 EDN: AWFBBA
  13. de Oliveira MR, Nabavi SF, Manayi A, et al. Resveratrol and the mitochondria: From triggering the intrinsic apoptotic pathway to inducing mitochondrial biogenesis, a mechanistic view. Biochim Biophys Acta. 2016;1860(4):727–45. doi: 10.1016/j.bbagen.2016.01.017
  14. Liu X, Zhao H, Jin Q, et al. Resveratrol induces apoptosis and inhibits adipogenesis by stimulating the SIRT1-AMPKα-FOXO1 signalling pathway in bovine intramuscular adipocytes. Mol Cell Biochem. 2018;439(1–2):213–223. doi: 10.1007/s11010-017-3149-z
  15. Shirinsky IV, Shirinsky VS, Filatova KYu. Efficacy and safety of curcumin in patients with metabolic phenotype of osteoarthritis: A pilot study. Medical Immunology. 2023;25(5):1099–1102. doi: 10.15789/1563-0625-EAS-2771 EDN: SGZLDD
  16. Xia ZH, Zhang SY, Chen YS, et al. Curcumin anti-diabetic effect mainly correlates with its anti-apoptotic actions and PI3K/Akt signal pathway regulation in the liver. Food Chem Toxicol. 2020;146:111803. doi: 10.1016/j.fct.2020.111803
  17. Accattato F, Greco M, Pullano SA, et al. Effects of acute physical exercise on oxidative stress and inflammatory status in young, sedentary obese subjects. PLoS One. 2017;12(6):e0178900. doi: 10.1371/journal.pone.0178900
  18. Zhang X, Gao F. Exercise improves vascular health: Role of mitochondria. Free Radic Biol Med. 2021;177:347–359. doi: 10.1016/j.freeradbiomed.2021.11.002
  19. Ghoweba RE, Khowailed AA, Aboulhoda BE, et al. Synergistic role of resveratrol and exercise training in management of diabetic neuropathy and myopathy via SIRT1/NGF/GAP43 linkage. Tissue Cell. 2023;81:102014. doi: 10.1016/j.tice.2023.102014
  20. Liao ZY, Chen JL, Xiao MH, et al. The effect of exercise, resveratrol or their combination on Sarcopenia in aged rats via regulation of AMPK/Sirt1 pathway. Exp Gerontol. 2017;98:177–183. doi: 10.1016/j.exger.2017.08.032
  21. Nagata I, Kawashima M, Miyazaki A, et al. Icing after skeletal muscle injury with necrosis in a small fraction of myofibers limits inducible nitric oxide synthase-expressing macrophage invasion and facilitates muscle regeneration. Am J Physiol Regul Integr Comp Physiol. 2023;324(4):R574–R588. doi: 10.1152/ajpregu.00258.2022
  22. Argilés JM, Busquets S, Stemmler B, López-Soriano FJ. Cachexia and sarcopenia: mechanisms and potential targets for intervention. Curr Opin Pharmacol. 2015;22:100–6. doi: 10.1016/j.coph.2015.04.003
  23. Chen TH, Koh KY, Lin KM, Chou CK. Mitochondrial Dysfunction as an Underlying Cause of Skeletal Muscle Disorders. Int J Mol Sci. 2022;23(21):12926. doi: 10.3390/ijms232112926
  24. Li W, Sang H, Xu X, et al. Protective effect of dihydromyricetin on vascular smooth muscle cell apoptosis induced by hydrogen peroxide in rats. Perfusion. 2023;38(3):491–500. doi: 10.1177/02676591211059901
  25. Sahoo G, Samal D, Khandayataray P, Murthy MK. A Review on Caspases: Key Regulators of Biological Activities and Apoptosis. Mol Neurobiol. 2023;60(10):5805–5837. doi: 10.1007/s12035-023-03433-5.
  26. Means RE, Katz SG. Balancing life and death: BCL-2 family members at diverse ER-mitochondrial contact sites. FEBS J. 2022;289(22):7075–7112. doi: 10.1111/febs.16241
  27. Mailloux RJ. An Update on Mitochondrial Reactive Oxygen Species Production. Antioxidants (Basel). 2020;9(6):472. doi: 10.3390/antiox9060472
  28. Napolitano G, Fasciolo G, Venditti P. Mitochondrial Management of Reactive Oxygen Species. Antioxidants (Basel). 2021;10(11):1824. doi: 10.3390/antiox10111824
  29. Collins KH, Herzog W, MacDonald GZ, et al. Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity. Front Physiol. 2018;9:112. doi: 10.3389/fphys.2018.00112
  30. Jin JY, Wei XX, Zhi XL, et al. Drp1-dependent mitochondrial fission in cardiovascular disease. Acta Pharmacol Sin. 2021;42(5):655–664. doi: 10.1038/s41401-020-00518-y
  31. Yapa NMB, Lisnyak V, Reljic B, Ryan MT. Mitochondrial dynamics in health and disease. FEBS Lett. 2021;595(8):1184–1204. doi: 10.1002/1873-3468.14077
  32. Berns SA, Sheptulina AF, Mamutova EM, et al. Sarcopenic obesity: epidemiology, pathogenesis and diagnostic criteria. Cardiovascular Therapy and Prevention. 2023;22(6):3576. (In Russ.) doi: 10.15829/1728-8800-2023-3576 EDN: OWOAYO
  33. Abrigo J, Rivera JC, Aravena J, et al. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis. Oxid Med Cell Longev. 2016;2016:9047821. doi: 10.1155/2016/9047821
  34. Reynaud O, Wang J, Ayoub MB, et al. The impact of high-fat feeding and parkin overexpression on skeletal muscle mass, mitochondrial respiration, and H2O2 emission. Am J Physiol Cell Physiol. 2023;324(2):C366–C376. doi: 10.1152/ajpcell.00388.2022
  35. Larsson L, Degens H, Li M, et al. Sarcopenia: Aging-Related Loss of Muscle Mass and Function. Physiol Rev. 2019;99(1):427–511. doi: 10.1152/physrev.00061.2017
  36. Merz KE, Thurmond DC. Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake. Compr Physiol. 2020;10(3):785–809. doi: 10.1002/cphy.c190029
  37. Ou MY, Zhang H, Tan PC, et al. Adipose tissue aging: mechanisms and therapeutic implications. Cell Death Dis. 2022;13(4):300. doi: 10.1038/s41419-022-04752-6
  38. Dungan CM, Li J, Williamson DL. Caloric Restriction Normalizes Obesity-Induced Alterations on Regulators of Skeletal Muscle Growth Signaling. Lipids. 2016;51(8):905–12. doi: 10.1007/s11745-016-4168-3
  39. Sishi B, Loos B, Ellis B, et al. Diet-induced obesity alters signalling pathways and induces atrophy and apoptosis in skeletal muscle in a prediabetic rat model. Exp Physiol. 2011;96(2):179–93. doi: 10.1113/expphysiol.2010.054189
  40. Yuzefovych LV, Musiyenko SI, Wilson GL, Rachek LI. Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice. PLoS One. 2013;8(1):e54059. doi: 10.1371/journal.pone.0054059
  41. Turpin SM, Lancaster GI, Darby I, et al. Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance. Am J Physiol Endocrinol Metab. 2006;291(6):E1341–50. doi: 10.1152/ajpendo.00095.2006
  42. Peterson JM, Bryner RW, Alway SE. Satellite cell proliferation is reduced in muscles of obese Zucker rats but restored with loading. Am J Physiol Cell Physiol. 2008;295(2):C521–8. doi: 10.1152/ajpcell.00073.2008
  43. Peterson JM, Bryner RW, Sindler A, et al. Mitochondrial apoptotic signaling is elevated in cardiac but not skeletal muscle in the obese Zucker rat and is reduced with aerobic exercise. J Appl Physiol (1985). 2008;105(6):1934–43. doi: 10.1152/japplphysiol.00037.2008
  44. Romantsova TR, Sych YuP. Immunometabolism and metainflammation in obesity. Obesity and metabolism. 2019;16(4):3–17. doi: 10.14341/omet12218 EDN: GIFRWJ
  45. Vazeille E, Slimani L, Claustre A, et al. Curcumin treatment prevents increased proteasome and apoptosome activities in rat skeletal muscle during reloading and improves subsequent recovery. J Nutr Biochem. 2012;23(3):245–51. doi: 10.1016/j.jnutbio.2010.11.021
  46. Lee DY, Chun YS, Kim JK, et al. Curcumin Attenuates Sarcopenia in Chronic Forced Exercise Executed Aged Mice by Regulating Muscle Degradation and Protein Synthesis with Antioxidant and Anti-inflammatory Effects. J Agric Food Chem. 2021;69(22):6214–6228. doi: 10.1021/acs.jafc.1c00699
  47. Sin TK, Yu AP, Yung BY, et al. Effects of long-term resveratrol-induced SIRT1 activation on insulin and apoptotic signalling in aged skeletal muscle. Acta Diabetol. 2015;52(6):1063–75. doi: 10.1007/s00592-015-0767-3
  48. Wu J-P. Resveratrol attenuates obesity- and aging-induced sarcopenia mitochondrial dysfunction in mice skeletal muscle. FASEB J. 2020;34(S1):1–1. doi: 10.1096/fasebj.2020.34.s1.00044
  49. Wang D, Sun H, Song G, et al. Resveratrol Improves Muscle Atrophy by Modulating Mitochondrial Quality Control in STZ-Induced Diabetic Mice. Mol Nutr Food Res. 2018;62(9):e1700941. doi: 10.1002/mnfr.201700941
  50. Aslan A, Beyaz S, Gok O, Erman O. The effect of ellagic acid on caspase-3/bcl-2/Nrf-2/NF-kB/TNF-α /COX-2 gene expression product apoptosis pathway: a new approach for muscle damage therapy. Mol Biol Rep. 2020;47(4):2573–2582. doi: 10.1007/s11033-020-05340-7
  51. Wang D, Yang Y, Zou X, et al. Antioxidant Apigenin Relieves Age-Related Muscle Atrophy by Inhibiting Oxidative Stress and Hyperactive Mitophagy and Apoptosis in Skeletal Muscle of Mice. J Gerontol A Biol Sci Med Sci. 2020;75(11):2081–2088. doi: 10.1093/gerona/glaa214
  52. Le NH, Kim CS, Park T, et al. Quercetin protects against obesity-induced skeletal muscle inflammation and atrophy. Mediators Inflamm. 2014;2014:834294. doi: 10.1155/2014/834294
  53. Chen C, Yang JS, Lu CC, et al. Effect of Quercetin on Dexamethasone-Induced C2C12 Skeletal Muscle Cell Injury. Molecules. 2020;25(14):3267. doi: 10.3390/molecules25143267
  54. Tabata S, Aizawa M, Kinoshita M, et al. The influence of isoflavone for denervation-induced muscle atrophy. Eur J Nutr. 2019;58(1):291–300. doi: 10.1007/s00394-017-1593-x
  55. Mallardo M, Daniele A, Musumeci G, Nigro E. A Narrative Review on Adipose Tissue and Overtraining: Shedding Light on the Interplay among Adipokines, Exercise and Overtraining. Int J Mol Sci. 2024;25(7):4089. doi: 10.3390/ijms25074089
  56. Taherkhani S, Valaei K, Arazi H, Suzuki K. An Overview of Physical Exercise and Antioxidant Supplementation Influences on Skeletal Muscle Oxidative Stress. Antioxidants (Basel). 2021;10(10):1528. doi: 10.3390/antiox10101528
  57. Nikawa T, Ulla A, Sakakibara I. Polyphenols and Their Effects on Muscle Atrophy and Muscle Health. Molecules. 2021;26(16):4887. doi: 10.3390/molecules26164887
  58. Fernández-Sánchez A, Madrigal-Santillán E, Bautista M, et al. Inflammation, oxidative stress, and obesity. Int J Mol Sci. 2011;12(5):3117–32. doi: 10.3390/ijms12053117
  59. Heo JW, No MH, Cho J, et al. Moderate aerobic exercise training ameliorates impairment of mitochondrial function and dynamics in skeletal muscle of high-fat diet-induced obese mice. FASEB J. 2021;35(2):e21340. doi: 10.1096/fj.202002394R
  60. Kim HJ, Kwon O. Aerobic exercise prevents apoptosis in skeletal muscles of high-fat-fed ovariectomized rats. Phys Act Nutr. 2022;26(2):1–7. doi: 10.20463/pan.2022.0007
  61. Cho DK, Choi DH, Cho JY. Effect of treadmill exercise on skeletal muscle autophagy in rats with obesity induced by a high-fat diet. J Exerc Nutrition Biochem. 2017;21(3):26–34. doi: 10.20463/jenb.2017.0013
  62. Lee SD, Shyu WC, Cheng IS, et al. Effects of exercise training on cardiac apoptosis in obese rats. Nutr Metab Cardiovasc Dis. 2013;23(6):566–73. doi: 10.1016/j.numecd.2011.11.002
  63. Pattanakuhar S, Sutham W, Sripetchwandee J, et al. Combined exercise and calorie restriction therapies restore contractile and mitochondrial functions in skeletal muscle of obese-insulin resistant rats. Nutrition. 2019;62:74–84. doi: 10.1016/j.nut.2018.11.031
  64. Wohlgemuth SE, Seo AY, Marzetti E, et al. Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Exp Gerontol. 2010;45(2):138–48. doi: 10.1016/j.exger.2009.11.002
  65. Di Meo S, Napolitano G, Venditti P. Mediators of Physical Activity Protection against ROS-Linked Skeletal Muscle Damage. Int J Mol Sci. 2019;20(12):3024. doi: 10.3390/ijms20123024
  66. Sharma VK, Singh TG, Singh S, Garg N, Dhiman S. Apoptotic Pathways and Alzheimer’s Disease: Probing Therapeutic Potential. Neurochem Res. 2021;46(12):3103–3122. doi: 10.1007/s11064-021-03418-7
  67. Veras ASC, Correia RR, Batista VRG, et al. Aerobic physical exercise modifies the prostate tumoral environment. Life Sci. 2023;332:122097. doi: 10.1016/j.lfs.2023.122097
  68. Naoi M, Wu Y, Shamoto-Nagai M, Maruyama W. Mitochondria in Neuroprotection by Phytochemicals: Bioactive Polyphenols Modulate Mitochondrial Apoptosis System, Function and Structure. Int J Mol Sci. 2019;20(10):2451. doi: 10.3390/ijms20102451
  69. Yan Z, Lira VA, Greene NP. Exercise training-induced regulation of mitochondrial quality. Exerc Sport Sci Rev. 2012;40(3):159–64. doi: 10.1097/JES.0b013e3182575599
  70. Forbes-Hernández TY, Giampieri F, Gasparrini M, et al. The effects of bioactive compounds from plant foods on mitochondrial function: a focus on apoptotic mechanisms. Food Chem Toxicol. 2014;68:154–82. doi: 10.1016/j.fct.2014.03.017
  71. Slavin MB, Khemraj P, Hood DA. Exercise, mitochondrial dysfunction and inflammasomes in skeletal muscle. Biomed J. 2024;47(1):100636. doi: 10.1016/j.bj.2023.100636
  72. Shehata AH, Anter AF, Ahmed AF. Role of SIRT1 in sepsis-induced encephalopathy: Molecular targets for future therapies. Eur J Neurosci. 2023;58(10):4211–4235. doi: 10.1111/ejn.16167
  73. Yang L, Liu D, Jiang S, et al. SIRT1 signaling pathways in sarcopenia: Novel mechanisms and potential therapeutic targets. Biomed Pharmacother. 2024;177:116917. doi: 10.1016/j.biopha.2024.116917
  74. Zhang T, Xu L, Guo X, et al. The potential of herbal drugs to treat heart failure: The roles of Sirt1/AMPK. J Pharm Anal. 2024;14(2):157–176. doi: 10.1016/j.jpha.2023.09.001

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