مجله دانشگاه علوم پزشکی سبزوار

شماره جاری

بر اساس شماره‌های نشریه

بر اساس نویسندگان

بر اساس موضوعات

نمایه نویسندگان

نمایه کلیدواژه ها

درباره نشریه

اهداف و چشم انداز

اعضای هیات تحریریه

اصول اخلاقی انتشار مقاله

بانک ها و نمایه نامه ها

پیوندهای مفید

فرایند پذیرش مقالات

اخبار و اعلانات

فرم های ضروری نشریه

راهنمای تنظیم مقاله

راهنمای نگارش خلاصه سیاستی

فرم خلاصه سیاستی

ایریسین: یک کاندید برای درمان افسردگی

نوع مقاله : مروری

نویسندگان

1 کارشناس ارشد روان‌شناسی عمومی، دانشکده روان‌شناسی، دانشگاه پیام نور، تهران، ایران

2 استاد روانشناسی سلامت، دانشکده روان‌شناسی، دانشگاه پیام نور، تهران، ایران

چکیده

زمینه و هدف: ایریسین یک میوکاین است که در پاسخ به فعالیت فیزیکی از سلول­های عضلانی ترشح می­شود. در سال­های اخیر ارتباط بین ایریسین و افسردگی مورد مطالعه قرار گرفته است.
مواد و روش­ها: در این پژوهش، تعدادی از مطالعات موجود در زمینه ایریسین از طریق جستجوی الکترونیکی با واردکردن کلیدواژه­های ایریسین و افسردگی در بانک­های اطلاعاتی نظیر Google scholar، Google و PubMed بین سال­های 1990 تا 2024 نقد و بررسی شدند.
یافته­ها: نتایج نشان داد که ایریسین از سد خونی- مغزی عبور می­کند و منجر به فعال­سازی برخی از مسیرهای درون‌سلولی می­شود که با تغییر متابولیسم گلوکز از طریق مسیر گلیکولیز، چرخه کربس، گلیکوژن موجب بهبود علائم افسردگی می­شود. هم­چنین، ایریسین موجب فعال­سازی مسیر BNDF می­شود که ممکن است برخی از تأثیرات ایریسین بر افسردگی را وساطت کند. نتایج مطالعات بر انسان نتایج قابل متناقض را در ارتباط با سطح ایریسین و افسردگی گزارش کرده­اند.
نتیجه‌گیری: نتایج مطالعه حاضر نشان می­دهد اگرچه مطالعات در سطح سلول و مدل­های حیوانی بسیار امیدوارکننده هستند لیکن مطالعات در انسان نیاز به بررسی­های بیشتر دارند؛ از این رو، مطالعات بیشتر برای درک ارتباط بین ایریسین و افسردگی پیشنهاد می­شود.

تازه های تحقیق

https://scholar.google.com/citations?hl=en&user=Jj3bMXQAAAAJ

https://www.ncbi.nlm.nih.gov/sites/myncbi/leyla.haghighi%20kaffash.1/collections/64157063/public/

https://scholar.google.com/citations?user=76MfexUAAAAJ&hl=en

https://www.ncbi.nlm.nih.gov/sites/myncbi/mojgan.agah.1/collections/64159872/public/

 

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

Irisin: A Candidate for the Treatment of Depression

نویسندگان [English]

  • Leyla Haghighi Kaffash 1
  • Mojgan Agahheris 2

1 Master of Science in General Psychology, Faculty of Psychology, Payam Noor University, Tehran, Iran

2 Professor of Health Psychology, Faculty of Psychology, Payam Noor University, Tehran, Iran

چکیده [English]

Introduction: Irisin, a myokine released in response to physical activity, has garnered interest due to its potential connection to depression. This study aims to comprehensively review the existing research on the relationship between irisin and depression.
Materials and Methods: A systematic search was conducted to identify studies investigating irisin levels in individuals with depression. Keyword searches for "irisin" and "depression" were performed in databases such as Google Scholar, Google, and PubMed from 1990 to 2024.
Results: The findings suggest that irisin can traverse the blood-brain barrier, activating intracellular pathways that may alleviate depression symptoms by regulating glucose metabolism through glycolysis, the Krebs cycle, and glycogen pathways. Furthermore, irisin is implicated in activating the BDNF pathway, which may play a role in mediating its effects on depression. However, human studies present conflicting results regarding irisin levels and their relationship to depression.
Conclusion: While promising results have been observed in cell and animal studies, further research involving human subjects is necessary to fully understand the complex relationship between irisin and depression. Additional investigations are recommended to enhance our understanding of this field.

کلیدواژه‌ها [English]

  • Irisin
  • Major depression
  • PGC1α
مراجع
  1. Bromet E, Andrade L, Hwang I, Sampson N, Alonso J, De Girolamo G. others.(2011). Cross-national epidemiology of DSM-IV major depressive episode. BMC Medicine.9(1):90. DOI: 10.1186/1741-7015-9-90
  2. Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al. Major depressive disorder. Nature reviews Disease primers. 2016;2(1):1-20. Doi: 10.1038/nrdp.2016.65.
  3. Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. The lancet. 2013;382(9904):1575-86. Doi: 10.1016/S0140-6736(13)61611-6.
  4. Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al. Major depressive disorder. Nat Rev Dis Primers. 2016;2:16065. Doi: 10.1038/nrdp.2016.65.
  5. De Felice FG, Gonçalves RA, Ferreira ST. Impaired insulin signalling and allostatic load in Alzheimer disease. Nat Rev Neurosci. 2022;23(4):215-30. Doi: 10.1038/s41583-022-00558-9.
  6. Selles MC, Oliveira MM, Ferreira ST. Brain Inflammation Connects Cognitive and Non-Cognitive Symptoms in Alzheimer's Disease. J Alzheimers Dis. 2018;64(s1):S313-s27. Doi: 10.3233/JAD-179925.
  7. Jo D, Song J. Irisin acts via the PGC-1α and BDNF pathway to improve depression-like behavior. Clinical Nutrition Research. 2021;10(4):292. Doi: 10.7762/cnr.2021.10.4.292.
  8. Wrann C, White J, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, et al. Exercise induces hippocampal BDNF through a PGC-1alpha. FNDC5 Pathway Cell Metab. 2013;18:649659. doi: 10.1016/j.cmet.2013.09.008.
  9. Huh JY, Mougios V, Kabasakalis A, Fatouros I, Siopi A, Douroudos II, et al. Exercise-induced irisin secretion is independent of age or fitness level and increased irisin may directly modulate muscle metabolism through AMPK activation. The Journal of Clinical Endocrinology & Metabolism. 2014;99(11):E2154-E61 Doi: 10.1210/jc.2014-1437.
  10. Elsen M, Raschke S, Eckel J. Browning of white fat: does irisin play a role in humans. J endocrinol. 2014;222(1):R25-38. Doi: 10.1530/JOE-14-0189
  11. Phillips C, Baktir MA, Srivatsan M, Salehi A. Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Frontiers in cellular neuroscience. 2014;8:170. Doi: 10.3389/fncel.2014.00170
  12. Xia D-Y, Huang X, Bi C-F, Mao L-L, Peng L-J, Qian H-R. PGC-1α or FNDC5 is involved in modulating the effects of Aβ1− 42 oligomers on suppressing the expression of BDNF, a beneficial factor for inhibiting neuronal apoptosis, Aβ deposition and cognitive decline of APP/PS1 Tg mice. Frontiers in aging neuroscience. 2017;9:65. Doi: 10.3389/fnagi.2017.00065.
  13. Wang K, Li H, Wang H, Wang J-h, Song F, Sun Y. Irisin exerts neuroprotective effects on cultured neurons by regulating astrocytes. Mediators of inflammation. 2018;2018. Doi: 10.1155/2018/9070341.
  14. Kempuraj D, Thangavel R, Natteru P, Selvakumar G, Saeed D, Zahoor H, et al. Neuroinflammation induces neurodegeneration. Journal of neurology, neurosurgery and spine. 2016;1(1). PMCID: PMC5260818
  15. Dun SL, Lyu R-M, Chen Y-H, Chang J-K, Luo JJ, Dun NJ. Irisin-immunoreactivity in neural and non-neural cells of the rodent. Neuroscience. 2013;240:155-62. Doi: 10.1016/j.neuroscience.2013.02.050
  16. Piya MK, Harte AL, Sivakumar K, Tripathi G, Voyias PD, James S, et al. The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes. American Journal of Physiology-Endocrinology and Metabolism. 2014;306(5):E512-E8. Doi: 10.1152/ajpendo.00308.2013
  17. Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell metabolism. 2013;18(5):649-59. Doi: 10.1016/j.cmet.2013.09.008
  18. Park DI, Novak B, Yan Y, Kaya ME, Turck CW. Paroxetine binding and activation of phosphofructokinase implicates energy metabolism in antidepressant mode of action. Journal of Psychiatric Research. 2020;129:8-14. Doi: 10.1016/j.jpsychires.2020.05.033
  19. Jiang H, Niu F, Zheng Y, Xu Y. CART mitigates oxidative stress and DNA damage in memory deficits of APP/PS1 mice via upregulating β‑amyloid metabolism‑associated enzymes. Molecular Medicine Reports. 2021;23(4):1-12. Doi: 10.3892/mmr.2021.11919
  20. Park DI, Novak B, Yan Y, Kaya ME, Turck CW. Paroxetine binding and activation of phosphofructokinase implicates energy metabolism in antidepressant mode of action. J Psychiatr Res. 2020;129:8-14. Doi: 10.1016/j.jpsychires.2020.05.033.
  21. Chan SY, Probert F, Radford-Smith DE, Hebert JC, Claridge TD, Anthony DC, Burnet PW. Post-inflammatory behavioural despair in male mice is associated with reduced cortical glutamate-glutamine ratios, and circulating lipid and energy metabolites. Scientific Reports. 2020;10(1):16857. Doi: 10.1038/s41598-020-74008-w.
  22. Nasca C, Dobbin J, Bigio B, Watson K, de Angelis P, Kautz M, et al. Insulin receptor substrate in brain-enriched exosomes in subjects with major depression: on the path of creation of biosignatures of central insulin resistance. Molecular psychiatry. 2021;26(9):5140-9. Doi: 10.1038/s41380-020-0804-7.
  23. Rezin GT, Amboni G, Zugno AI, Quevedo J, Streck EL. Mitochondrial dysfunction and psychiatric disorders. Neurochemical research. 2009;34:1021-9. Doi: 10.1007/s11064-008-9865-8
  24. Videbech P. PET measurements of brain glucose metabolism and blood flow in major depressive disorder: a critical review. Acta Psychiatrica Scandinavica. 2000;101(1):11-20 Doi: 10.1034/j.1600-0447.2000.101001011.x..
  25. Chen J-J, Xie J, Li W-W, Bai S-J, Wang W, Zheng P, Xie P. Age-specific urinary metabolite signatures and functions in patients with major depressive disorder. Aging (Albany NY). 2019;11(17):6626. Doi: 10.18632/aging.102133
  26. Obel LF, Müller MS, Walls AB, Sickmann HM, Bak LK, Waagepetersen HS, Schousboe A. Brain glycogen—new perspectives on its metabolic function and regulation at the subcellular level. Frontiers in neuroenergetics. 2012;4:3. Doi: 10.3389/fnene.2012.00003
  27. Bélanger M, Allaman I, Magistretti PJ. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell metabolism. 2011;14(6):724-38. Doi: 10.1016/j.cmet.2011.08.016.
  28. Bekhbat M, Treadway MT, Goldsmith DR, Woolwine BJ, Haroon E, Miller AH, Felger JC. Gene signatures in peripheral blood immune cells related to insulin resistance and low tyrosine metabolism define a sub-type of depression with high CRP and anhedonia. Brain, behavior, and immunity. 2020;88:161-5. Doi: 10.1016/j.bbi.2020.03.015.
  29. Roy T, Lloyd CE. Epidemiology of depression and diabetes: a systematic review. Journal of affective disorders. 2012;142:S8-S21. Doi: 10.1016/S0165-0327(12)70004-6
  30. Demyttenaere K, De Fruyt J, Stahl SM. The many faces of fatigue in major depressive disorder. International Journal of Neuropsychopharmacology. 2005;8(1):93-105. Doi: 10.1017/S1461145704004729.
  31. Cao X, Li L-P, Wang Q, Wu Q, Hu H-H, Zhang M, et al. Astrocyte-derived ATP modulates depressive-like behaviors. Nature medicine. 2013;19(6):773-7. Doi: 10.1038/nm.3162.
  32. Allaman I, Bélanger M, Magistretti PJ. Astrocyte–neuron metabolic relationships: for better and for worse. Trends in neurosciences. 2011;34(2):76-87 Doi: 10.1016/j.tins.2010.12.001..
  33. Madrigal JL, Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Rodrigo J, Leza JC. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology. 2001;24(4):420-9. Doi: 10.1016/S0893-133X(00)00208-6
  34. Wang L, Song J, Wang C, Lin P, Liang K, Sun Y, et al. Circulating levels of betatrophin and irisin are not associated with pancreatic β-cell function in previously diagnosed type 2 diabetes mellitus patients. Journal of diabetes research. 2016;2016 Doi: 10.1155/2016/2616539.
  35. Spiegelman BM, editor Transcriptional control of mitochondrial energy metabolism through the PGC1 coactivators. Mitochondrial Biology: New Perspectives: Novartis Foundation Symposium 287; 2007: Wiley Online Library. Doi: 10.1152/ajpendo.00666.2007
  36. Leick L, Wojtaszewski JF, Johansen ST, Kiilerich K, Comes G, Hellsten Y, et al. PGC-1α is not mandatory for exercise-and training-induced adaptive gene responses in mouse skeletal muscle. American journal of physiology-endocrinology and metabolism. 2008;294(2):E463-E74.
  37. Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic peroxisome proliferator-activated receptor γ (PPARγ) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. Journal of Biological Chemistry. 2010;285(10):7153-64. Doi: 10.1074/jbc.M109.053942
  38. Zsuga J, Tajti G, Papp C, Juhasz B, Gesztelyi R. FNDC5/irisin, a molecular target for boosting reward-related learning and motivation. Medical Hypotheses. 2016;90:23-8. Doi: 10.1016/j.mehy.2016.02.020
  39. Carvalho AF, Rocha DQ, McIntyre RS, Mesquita LM, Koehler CA, Hyphantis TN, et al. Adipokines as emerging depression biomarkers: a systematic review and meta-analysis. Journal of psychiatric research. 2014;59:28-37. Doi: 10.1016/j.jpsychires.2014.08.002.
  40. Wang S, Pan J. Irisin ameliorates depressive-like behaviors in rats by regulating energy metabolism. Biochemical and biophysical research communications. 2016;474(1):22-8. Doi: 10.1016/j.bbrc.2016.04.047.
  41. Schuch FB, Vancampfort D, Richards J, Rosenbaum S, Ward PB, Stubbs B. Exercise as a treatment for depression: a meta-analysis adjusting for publication bias. Journal of psychiatric research. 2016;77:42-51. Doi: 10.1016/j.jpsychires.2016.02.023
  42. Siteneski A, Cunha MP, Lieberknecht V, Pazini FL, Gruhn K, Brocardo PS, Rodrigues ALS. Central irisin administration affords antidepressant-like effect and modulates neuroplasticity-related genes in the hippocampus and prefrontal cortex of mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018;84:294-303. Doi: 10.1016/j.pnpbp.2018.03.004.
  43. Maia TV. Reinforcement learning, conditioning, and the brain: Successes and challenges. Cognitive, Affective, & Behavioral Neuroscience. 2009;9(4):343-64. Doi: 10.3758/CABN.9.4.343
  44. Yan Q-S, Feng M-J, Yan S-E. Different expression of brain-derived neurotrophic factor in the nucleus accumbens of alcohol-preferring (P) and-nonpreferring (NP) rats. Brain research. 2005;1035(2):215-8. Doi: 10.1016/j.brainres.2004.12.039.
  45. Zsuga J, Biro K, Papp C, Tajti G, Gesztelyi R. The “proactive” model of learning: Integrative framework for model-free and model-based reinforcement learning utilizing the associative learning-based proactive brain concept. Behavioral Neuroscience. 2016;130(1):6. Doi: 10.1037/bne0000116.
  46. Ieraci A, Madaio AI, Mallei A, Lee FS, Popoli M. Brain-derived neurotrophic factor Val66Met human polymorphism impairs the beneficial exercise-induced neurobiological changes in mice. Neuropsychopharmacology. 2016;41(13):3070-9. Doi: 10.1038/npp.2016.120
  47. Nestler EJ, Carlezon Jr WA. The mesolimbic dopamine reward circuit in depression. Biological psychiatry. 2006;59(12):1151-9. Doi: 10.1016/j.biopsych.2005.09.018
  48. Huys QJ, Pizzagalli DA, Bogdan R, Dayan P. Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis. Biol Mood Anxiety Disord. 2013;3(1):12. Doi: 10.1186/2045-5380-3-12
  49. Qin L, Bouchard R, Pugazhenthi S. Regulation of cyclic AMP response element-binding protein during neuroglial interactions. J Neurochem. 2016;136(5):918-30. Doi: 10.1111/jnc.13497. Epub 2016 Jan 11
  50. Suri D, Vaidya VA. Glucocorticoid regulation of brain-derived neurotrophic factor: relevance to hippocampal structural and functional plasticity. Neuroscience. 2013;239:196-213. Doi: 10.1016/j.neuroscience.2012.08.065
  51. Jeanneteau F, Deinhardt K, Miyoshi G, Bennett AM, Chao MV. The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching. Nat Neurosci. 2010;13(11):1373-9. Doi: 10.1038/nn.2655. Epub 2010 Oct 10
  52. Dong Y, Pu K, Duan W, Chen H, Chen L, Wang Y. Involvement of Akt/CREB signaling pathways in the protective effect of EPA against interleukin-1β-induced cytotoxicity and BDNF down-regulation in cultured rat hippocampal neurons. BMC Neurosci. 2018;19(1):52. Doi: 10.1186/s12868-018-0455-7.
  53. Li X, Jope RS. Is glycogen synthase kinase-3 a central modulator in mood regulation? Neuropsychopharmacology. 2010;35(11):2143-54. Doi: 10.1038/npp.2010.105. Epub 2010 Jul 28.
  54. Ihara K, Yoshida H, Jones PB, Hashizume M, Suzuki Y, Ishijima H, et al. Serum BDNF levels before and after the development of mood disorders: a case-control study in a population cohort. Transl Psychiatry. 2016;6(4):e782. Doi: 10.1038/tp.2016.47.
  55. Brunoni AR, Lopes M, Fregni F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. The The International Journal of Neuropsychopharmacology. 2008;11(8):1169-80. Doi: 10.1017/S1461145708009309. Epub 2008 Aug 28.
  56. Kheirouri S, Noorazar SG, Alizadeh M, Dana-Alamdari L. Elevated brain-derived neurotrophic factor correlates negatively with severity and duration of major depressive episodes. Cognitive and Behavioral Neurology. 2016;29(1):24-31. Doi: 10.1097/WNN.0000000000000089
  57. Babaei A, Nourshahi M, Fani M, Entezari Z, Jameie SB, Haghparast A. The effectiveness of continuous and interval exercise preconditioning against chronic unpredictable stress: Involvement of hippocampal PGC-1α/FNDC5/BDNF pathway. J Psychiatr Res. 2021;136:173-83. Doi: 10.1016/j.jpsychires.2021.02.006. Epub 2021 Feb 13
  58. Wu Y, Sun F, Guo Y, Zhang Y, Li L, Dang R, Jiang P. Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway. Behav Neurol. 2021;2021:2630445 Doi: 10.1155/2021/2630445. eCollection 2021.
  59. Siteneski A, Cunha MP, Lieberknecht V, Pazini FL, Gruhn K, Brocardo PS, Rodrigues ALS. Central irisin administration affords antidepressant-like effect and modulates neuroplasticity-related genes in the hippocampus and prefrontal cortex of mice. Prog Neuropsychopharmacol Biol Psychiatry. 2018;84(Pt A):294-303. Doi: 10.1016/j.pnpbp.2018.03.004. Epub 2018 Mar 7.
  60. Lima-Filho R, Fortuna JS, Cozachenco D, Isaac AR, Lyra ESN, Saldanha A, et al. Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression. eNeuro. 2023;10(2). Doi: 10.1523/ENEURO.0256-22.2023
  61. Hou Z, Zhang J, Yu K, Song F. Irisin ameliorates the postoperative depressive-like behavior by reducing the surface expression of epidermal growth factor receptor in mice. Neurochemistry International. 2020;135:104705.. Doi: 10.1016/j.neuint.2020.104705. Epub 2020 Feb 8.
  62. Tu WJ, Qiu HC, Liu Q, Li X, Zhao JZ, Zeng X. Decreased level of irisin, a skeletal muscle cell-derived myokine, is associated with post-stroke depression in the ischemic stroke population. J Neuroinflammation. 2018;15(1):133. DOI: 10.1186/s12974-018-1177-6
  63. Han W, Zhang C, Wang H, Yang M, Guo Y, Li G, et al. Alterations of irisin, adropin, preptin and BDNF concentrations in coronary heart disease patients comorbid with depression. Ann Transl Med. 2019;7(14):298. Doi: 10.21037/atm.2019.05.77.
  64. Hofmann T, Elbelt U, Ahnis A, Obbarius A, Rose M, Klapp BF, Stengel A. The exercise-induced myokine irisin does not show an association with depressiveness, anxiety and perceived stress in obese women. J Physiol Pharmacol. 2016;67(2):195-203. PMID: 27226179
  65. Islam MR, Valaris S, Young MF, Haley EB, Luo R, Bond SF, et al. Exercise hormone irisin is a critical regulator of cognitive function. Nat Metab. 2021;3(8):1058-70. Doi: 10.1038/s42255-021-00438-z. Epub 2021 Aug 20
  66. Erzin G, Yüksel RN, Usta MB, Topçuoğlu C, Örsel S. Assessment of irisin levels in patients with bipolar depression and unipolar depression. Annals of Clinical and Analytical Medicine. 2020;27:7-4.
  67. Hofmann T, Elbelt U, Ahnis A, Obbarius A, Rose M, Klapp B, Stengel A. The exercise-induced myokine irisin does not show an association with depressiveness, anxiety and perceived stress in obese PMID: 27226179
  68. Mucher P, Batmyagmar D, Perkmann T, Repl M, Radakovics A, Ponocny‐Seliger E, et al. Basal myokine levels are associated with quality of life and depressed mood in older adults. Psychophysiology. 2021;58(5):e13799. Doi: 10.1111/psyp.13799. Epub 2021 Mar 2
مجله دانشگاه علوم پزشکی سبزوار
دوره 31، شماره 6
بهمن و اسفند 1403
صفحه 845-853
فایل ها
سابقه مقاله
  • تاریخ دریافت: 13 خرداد 1403
  • تاریخ بازنگری: 17 خرداد 1403
  • تاریخ پذیرش: 27 خرداد 1403
هم رسانی
ارجاع به این مقاله
آمار