دانشور پزشکی

دانشور پزشکی

اثر دو نوع تمرین (تداومی و تناوبی) و داروی آترواستاتین بر بیان ژن‌های VEGF و MMP2 بافت آئورت موش‌های سفید بزرگ آزمایشگاهی مدل دیابتی

نوع مقاله : مقاله پژوهشی

نویسندگان
مریم موسی پور 1
پروین فرزانگی 1
هاجر عباس زاده 1
فرزانه فرخی 2
1 گروه فیزیولوژی ورزشی، واحد ساری، دانشگاه آزاد اسلامی، ساری، ایران
2 گروه علوم و فناوری های زیستی، واحد ساری، دانشگاه آزاد اسلامی، ساری، ایران
10.22070/daneshmed.2024.18171.1393
چکیده
مقدمه و هدف: نشان داده شده است که حدود 80 درصد مرگ و میر در بیماران دیابتی ناشی از اختلالات قلبی عروقی است که به آن بیماری قلبی دیابتی گفته می‌شود، هدف از پژوهش حاضر بررسی اثر دو نوع تمرین (تداومی و تناوبی) و داروی آترواستاتین بر بیان ژن‌های VEGF و MMP2 بافت آئورت موش‌های سفید بزرگ آزمایشگاهی مدل دیابتی بود.
مواد و روش ها: 40 سر موش سفید بزرگ آزمایشگاهی نر، که در 8 گروه به‌صورت تصادفی تقسیم‌بندی شدند: شامل 1) کنترل، 2) دیابتی، 3) دیابتی+ تداومی، 4) دیابتی+ تناوبی، 5) آترواستاتین، 6) تداومی+ آترواستاتین، 7) تناوبی+ آترواستاتین و 8) سالین. موش‌های سفید بزرگ آزمایشگاهی دو نوع تمرین تداومی و تناوبی را 5 روز در هفته و به مدت 8 هفته اجرا کردند. آترواستاتین به‌صورت روزانه با دوز 20 میلی‌گرم به ازای هر کیلوگرم وزن بدن به‌صورت درون صفاقی به آنان تزریق شد. به‌منظور تعیین معنادار‌بودن تفاوت بین گروه‌ها از تحلیل واریانس یک‌طرفه و آزمون تعقیبی توکی استفاده شد.
نتایج: سطوح MMP2 گروه دیابت در سطح معناداری 05/0 نسبت به گروه کنترل افزایش معنا‌دار، و گروه‌های مکمل، تناوبی، تناوبی-مکمل و تداومی-مکمل نسبت به گروه دیابت کاهش معناداری یافت. سطوح VEGF گروه دیابت نسبت به گروه کنترل افزایش معنادار و گروه تناوبی-مکمل نسبت به گروه دیابت کاهش معنادار یافت.
نتیجه‌گیری: این احتمال وجود دارد که تمرین تناوبی در ترکیب با آترواستاتین بتواند از طریق کاهش ژن‌های VEGF و MMP2 بافت آئورت و بهبود آنژیوژنز که در اثر القای دیابت مختل شده بود، دارای اثر حفاظتی بر آئورت باشد.
کلیدواژه‌ها
تمرینات تداومی و تناوبی
آترواستاتین
آنژیوژنز
VEGF و MMP2
موضوعات
  1. Wang Y, Zhu J. Chen J, Xu R, Groth T, Wan H, et al. The signaling pathways induced by exosomes in promoting diabetic wound healing: a mini-review. Current Issues in Molecular Biology 2022; (44)10:4960–
  2. Ghaffari R, Salimi Rad M. Effect of exercise and non-exercise interventions on cardiac angiogenesis in diabetes mellitus patients: a review. International Journal of Diabetes and Endocrinology 2022;7(1).
  3. Rawal Sh, Ram TP, Coffey S, Williams M J A, Saxena P, Bunton RW, et al. Differential expression pattern of cardiovascular microRNAs in the human type-2 diabetic heart with normal ejection fraction. International Journal of Cardiology 2016; 202:40-43.
  4. Asmal AC, Leary WP, Thandroyen F. Diabetic heart disease. South African Medical Journal 1980; 57(19):788-790.
  5. Rask-Madsen Ch, King G L. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metabolism 2013; 17(1):20-33.
  6. Robert D G, Tepper O M, Pelo C R, Bhatt K A, Callaghan M, Bastidas N, et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. The American Journal of Pathology 2004; 164(6): 1935-1947.
  7. Asgari R, Vaisi-Raygani A, Aleagha MS, Mohammadi P, Bakhtiari M, Arghiani N. CD147 and MMPs as key factors in physiological and pathological processes. Biomedicine & Pharmacotherapy 2023;157: 113983.
  8. Chen Q, Jin M, Yang F, Zhu J, Xiao Q, Zhang L. Matrix metalloproteinases: inflammatory regulators of cell behaviors in vascular formation and remodeling. Mediators of Inflammation 2013:928315. doi: 10.1155/2013/928315.
  9. Rundhaug JE. Matrix metalloproteinases and angiogenesis. Journal of Cellular and Molecular Medicine 2005;9(2):267-85.
  10. Gialeli C, Theocharis AD, Karamanos NK. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. The FEBS Journal 2011;278(1):16-27.
  11. Silva Jr ND DA, Fernandes T, Soci UPR, Monteiro AW, Phillips MI, Edilamar Menezes DE Oliveira E M DE. Swimming training in rats increases cardiac MicroRNA-126 expression and angiogenesis. Medicine and Science in Sports and Exercise 2012;44(8):1453-62.
  12. Gibala M J, McGee S L. Metabolic adaptations to short-term high-intensity interval training: a little pain for a lot of gain?. Exercise and Sport Sciences Reviews 2008; 36(2):58-63.
  13. Sabzevari Rad R, Shirvani H, Mahmoodzadeh Hosseini H, Shamsoddini A, Samadi M. Micro RNA-126 promoting angiogenesis in diabetic heart by VEGF/Spred-1/Raf-1 pathway: effects of high-intensity interval training. Journal of Diabetes & Metabolic Disorders 2020; 19(2): 1089-1096.
  14. Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: Molecular mechanisms and clinical results. Trends in Molecular Medicine 2008; 14:37–44.
  15. Colhoun H M, Betteridge D J, Durrington, P N, Hitman G A, Neil H A, Livingstone S J, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicentre randomised placebo-controlled tri-al. Lancet 2004; 364: 685–696.
  16. Zhou J, Cheng M, Liao YH, Hu Y, Wu M, Wang, Q, et al. Rosuvastatin enhances angiogenesis via eNOS-dependent mobilization of endothelial progenitor cells. PLoS ONE 2013; 8: e63126.
  17. Garjani A; Rezazadeh H; Andalib S; Ziaee M; Doustar Y; Soraya H; et al. Ambivalent effects of atorvastatin on angiogenesis, epidermal cell proliferation and tumorgenesis in animal models. Biomedical Journal. 2012; 16:59–67.
  18. Mück AO, Seeger H, Wallwiener D. Class-specific pro-apoptotic effect of statins on human vascular endothelial cells. Z. Kardiol 2004; 93: 398–402.
  19. Wesołowska A, Winiarska H, Owoc J, Borowska M, Domagała J, Mikołajczak PŁ, et al. Effects of Low-Dose Atorvastatin on the Peripheral Blood Mononuclear Cell Secretion of Angiogenic Factors in Type 2 Diabetes. Biomolecules 2021;11(12):1885.
  20. Zeng H, Liu Zh. Atorvastatin Induces Hepatotoxicity in Diabetic Rats via Oxidative Stress, Inflammation, and Anti-Apoptotic Pathway. Medical Science Monitor 2019; 25: 6165-6173.
  21. Liu B, Peng XC, Zheng XL, Wang J, Qin YW. MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer 2009;66(2):169-75.
  22. Lin CJ, Lan YM, Ou MQ, Ji LQ, Lin SD. Expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer and its effect on angiogenesis of diabetic foot ulcer rats. Journal of endocrinological investigation. 2019;42(11):1307-17.
  23. Ahmad J, Zubair M, Malik A, Siddiqui MA, Wangnoo SK. Cathepsin-D, adiponectin, TNF-α, IL-6 and hsCRP plasma levels in subjects with diabetic foot and possible correlation with clinical variables: a multicentric study. The Foot 2012;22(3):194-9.
  24. Pakyari M, Farrokhi A, Maharlooei MK, Ghahary A. Critical role of transforming growth factor beta in different phases of wound healing. Advances in Wound Care 2013;2(5):215-24.
  25. Aida Y, Maeno M, Suzuki N, Shiratsuchi H, Motohashi M, Matsumura H. The effect of IL-1β on the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human chondrocytes. Life Sciences. 2005;77(25):3210-21.
  26. Rohani MG, Parks WC. Matrix remodeling by MMPs during wound repair. Matrix Biology 2015;44:113-21.
  27. Lv Y, Ge L, Zhao Y. Effect and mechanism of SHED on ulcer wound healing in Sprague-Dawley rat models with diabetic ulcer. Lancet 2004;364(9435):685-96.
  28. Jeon O, Song SJ, Bhang SH, Choi CY, Kim MJ, Kim BS. Additive effect of endothelial progenitor cell mobilization and bone marrow mononuclear cell transplantation on angiogenesis in mouse ischemic limbs. Journal of Biomedical Science 2007;14(3):323-30.
  29. Keating AM, Jacobs DS. Anti-VEGF treatment of corneal neovascularization. The Ocular Surface 2011;9(4):227-38.
  30. Kuhlencordt PJ, Rosel E, Gerszten RE, Morales-Ruiz M, Dombkowski D, Atkinson WJ, et al. Role of endothelial nitric oxide synthase in endothelial activation: insights from eNOS knockout endothelial cells. American Journal of Physiology-Cell Physiology 2004;286(5):C1195-202.
  31. Losi P, Briganti E, Errico C, Lisella A, Sanguinetti E, Chiellini F, et al. Fibrin-based scaffold incorporating VEGF-and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice. Acta Biomaterialia 2013 ;9(8):7814-21.
  32. Zhang EY, Gao B, Shi HL, Huang LF, Yang L, Wu XJ, et al. 20 (S)-Protopanaxadiol enhances angiogenesis via HIF-1α-mediated VEGF secretion by activating p70S6 kinase and benefits wound healing in genetically diabetic mice. Experimental & Molecular Medicine 2017;49(10):e387.
  33. Sunkari VG, Lind F, Botusan IR, Kashif A, Liu ZJ, Ylä-Herttuala S, et al. Hyperbaric oxygen therapy activates hypoxia-inducible factor 1 (HIF-1), which contributes to improved wound healing in diabetic mice. Wound Repair and Regeneration 2015;23(1):98-103.
  34. Zarezadehmehrizi A, Hong J, Lee J, Rajabi H, Gharakhanlu R, Naghdi N, et al. Exercise training ameliorates cognitive dysfunction in amyloid beta-injected rat model: possible mechanisms of Angiostatin/VEGF signaling. Metabolic Brain Disease 2021;36(8):2263-71.
  35. Pedrinolla A, Venturelli M, Fonte C, Tamburin S, Di Baldassarre A, Naro F, et al. Exercise training improves vascular function in patients with Alzheimer’s disease. European Journal of Applied Physiology 2020;120(10):2233-45.
  36. Guo H, Xia D, Liao S, Niu B, Tang J, Hu H, et al. Vascular endothelial growth factor improves the cognitive decline of Alzheimer’s disease via concurrently inducing the expression of ADAM10 and reducing the expression of β-site APP cleaving enzyme 1 in Tg2576 mice. Neuroscience Research 2019;142:49-57.
  37. Weis M, Heeschen C, Glassford A J, Cooke J P. Statins have biphasic effects on angiogenesis. Circulation 2002; 105:739–745.
  38. Zimering M B, Anderson R J, Ge Ling, Moritz T E. Increased plasma basic fibroblast growth factor is associated with coronary heart disease in adult type 2 diabetes mellitus. Metabolism 2011; 60:284–291.
  39. Khatri J J, Johnson C, Magid R, Lessner S M, Laude K M, Dikalov S I, Harrison D G; et al. Vascular oxidant stress enhances progression and angiogenesis of experimental atheroma. Circulation 2004; 109(4):520–525.
  40. Wang D, Li T, Wei H, Wang Y, Yang G, Tian Y, et al. Atorvastatin enhances angiogenesis to reduce subdural hematoma in a rat model. Journal of the neurological sciences 2016;362:91-9.
  41. Naduk-Kik J, Hrabec E. [The role of matrix metalloproteinases in the pathogenesis of diabetes mellitus and progression of diabetes retinopathy]. Postepy Hig Med Dosw (Online). 2008;62:442-50.
  42. Yan T, Chopp M, Ning R, Zacharek A, Roberts C, Chen J. Intracranial aneurysm formation in type-one diabetes rats. PloS One 2013;8:e67949.
  43. Amarenco P, Bogousslavsky J, Callahan A, 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. The New England Journal of Medicine 2006;355:549-59.
  44. Len K, Zuhl M. High intensity interval training vs. continuous cardio training: battle of the aerobic titans 2014.
  45. Hudlicka O, Brown MD. Adaptation of skeletal muscle microvasculature to increased or decreased blood flow: role of shear stress, nitric oxide and vascular endothelial growth factor. Journal of Vascular Research 2009;46(5):504-12.
  46. Ilkhanizadeh B, Shirpoor A, Khadem Ansari M H, Nemati S, Rasmi Y. Protective effects of ginger (Zingiber officinale) extract against diabetes-induced heart abnormality in rats. Diabetes & Metabolism Journal 2016;40(1):46-53.
  47. Ribatti D, Crivellato E. Mast cells, angiogenesis, and tumour growth. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2012;1822(1):2-8.
  48. Kadoglou NP, Vrabas IS, Sailer N, Kapelouzou A, Fotiadis G, Noussios G, et al. Exercise ameliorates serum MMP-9 and TIMP-2 levels in patients with type 2 diabetes. Diabetes & Metabolism 2010;36(2):144-51.
  49. Nazari M, Kordi MR, Choobineh S. The Effect of High Intensity Interval Training (HIIT) on Gelatinase-A (MMP-2) Serum Levels and Muscle Damage Indices in Young Sedentary Girls. Journal of Arak University of Medical Sciences 2015;18(1):78-86.
دانشور پزشکی
دوره 31، شماره 6 - شماره پیاپی 169
بهمن و اسفند 1402
صفحه 1-13