تاثیر هشت هفته تمرین هوازی همراه با مکمل یاری عصاره دانه انگور بر بیان VEGF و VEGFR-2 در بافت قلب رت های دیابتی شده با استرپتوزوسین

محورهای موضوعی : فصلنامه زیست شناسی جانوری

مریم شیرانی ¹ , جمشید بنایی بروجنی ² , سعید کشاورز ³ , محمد کریمی ⁴

1 - مرکز تحقیقات طب ورزشی، واحد نجف آباد، دانشگاه آزاد اسلامی، نجف آباد، ایران
2 - مرکز تحقیقات طب ورزشی، واحد نجف آباد، دانشگاه آزاد اسلامی، نجف آباد، ایران
3 - مرکز تحقیقات طب ورزشی، واحد نجف آباد، دانشگاه آزاد اسلامی، نجف آباد، ایران
4 - گروه تربیت بدنی و علوم ورزشی، دانشگاه صنعتی قم، قم، ایران

تاریخ دریافت : 1400/06/03 تاریخ پذیرش : 1400/07/03 تاریخ انتشار : 1401/06/01

کلید واژه: انگور, دیابت, آنژیوژنز, تمرین ورزشی,

چکیده مقاله :

پژوهش حاضر با هدف بررسی تاثیر هشت هفته تمرین هوازی به تنهایی یا همراه با مکمل یاری عصاره دانه انگور بر بیان VEGF و VEGFR-2 در بافت قلب رت های دیابتی شده با استرپتوزوسین (STZ) اجرا شده است. پژوهش حاضر از نوع بنیادی و تجربی می باشد. تعداد 32 سر رت ویستار نردیابتی به صورت تصادفی در چهار گروه هشت تایی شامل گروه های کنترل، مکمل، تمرین و تمرین+ مکمل تقسیم شدند.دیابت نوع1 با تزریق STZ به میزان 55 میلی گرم بر کیلوگرم وزن بدن القا شد. برنامه تمرین هوازی به مدت هشت هفته و پنج جلسه در هفته با شدت هفتاد درصد اجرا شد. مصرف عصاره هسته انگور نیز به صورت روزانه بود. بعد از دوره تمرینی موش ها کشته شده و بافت قلب جدا شد. بیان ژن های VEGF و VEGFR-2 در بافت قلب اندازه گیری شد. یافته های حاضر نشان داد که بیان VEGF بافت قلب در گروه های تمرین، مکمل و تمرین+مکمل در مقایسه با گروه کنترل به صورت معناداری بیشتر است (05/0 > p). علاوه بر این، بیان VEGFR-2 در گروه های تمرین و تمرین+مکمل در مقایسه با گروه کنترل و مکمل افزایش معناداری را نشان داد (05/0 >p ). نتایج حاضر نشان داد که تمرین هوازی به تنهایی و همراه با مکمل یاری عصاره هسته انگور نقش مهمی در افزایش بیان عوامل آنژیوژنیک در بافت قلب رت های دیابتی نوع1 دارد. باوجود این، مصرف عصاره هسته انگور به همراه تمرین هوازی نمی تواند تاثیر سینرژیک بر بیان VEGF و VEGFR-2 داشته باشد.

چکیده انگلیسی:

The angiogenesis process is disrupted in the heart tissue during diabetes. In contrast, exercise training is one of the effective factors on the angiogenesis process. The present study was conducted aiming at investigating the effect of eight weeks aerobic training alone or combined with grape seed extract supplementation on the myocardial expression of VEGF and VEGFR-2 in the streptozotocin-induced (STZ) diabetic rats. Thirty-two diabetic male Wistar rats with initial weight of 160-220 g were randomly assigned to four groups including control, supplement, training, and training + supplement groups, each consisting of eight rats. Type1 diabetes induced by STZ injection (55 mg/kg/bw). Aerobic training conducted for eight weeks and five sessions per week. Grape seed extract supplement was administrated by oral gavage at a dose of 40 mg/kg daily. Two day after the last training session or grape seed extract supplementation, all rats were anesthetized by means of ketamine–xylazine injection and their heart tissues were removed. VEGF and VEGFR-2 gene expression in the heart tissue were determined by Real-time PCR method and data were analyzed by SPSS software and one-way ANOVA test. The present study’s findings indicated that myocardial VEGF expression in training, supplement, and training + supplement groups were significantly higher compared to the control group (p<0.05). In addition, VEGFR-2 expression in training and training + supplement groups indicated a significant increase compared to control and supplement groups (p<0.05). The current study’s finding indicated that aerobic training alone and in combination with grape seed extract supplementation played a key role in increasing the expression of myocardial angiogenic factors in type 1 diabetic rats. However, consumption of grape seed extract along with aerobic training cannot have a synergistic effect on VEGF and VEGFR-2 expression.  

منابع و مأخذ:

1. Abhinand, C.S., Raju, R., Soumya, S.J., Arya, P.S., Sudhakaran, P.R. 2016. VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. Journal of cell communication and signaling, 10(4): 347-354.


2. Behl, T., Kotwani, A. 2015. Exploring the various aspects of the pathological role of vascular endothelial growth factor (VEGF) in diabetic retinopathy. Pharmacological Research, 99: 137-148.


3. Bugger, H., Abel, E.D. 2009. Rodent models of diabetic cardiomyopathy. Disease Models and Mechanisms, 2(9-10): 454-466.


4. Canavese, M., Altruda, F., Ruzicka, T., Schauber, J. 2010. Vascular endothelial growth factor (VEGF) in the pathogenesis of psoriasis—a possible target for novel therapies? Journal of Dermatological Science, 58(3): 171-176.


5. Carmeliet, P., Jain, R.K. 2000. Angiogenesis in cancer and other diseases. Nature, 407(6801), 249-257.


6. Chodari, L., Mohammadi, M., Ghorbanzadeh, V., Dariushnejad, H., Mohaddes, G. 2016. Testosterone and voluntary exercise promote angiogenesis in hearts of rats with diabetes by enhancing expression of VEGF-A and SDF-1a. Canadian Journal of Diabetes, 40(5): 436-441.


7. Chou, E., Suzuma, I., Way, K.J., Opland, D., Clermont, A.C., Naruse, K., Aiello, L.P. 2002. Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic States: a possible explanation for impaired collateral formation in cardiac tissue. Circulation, 105(3): 373-379.


8. Claesson-Welsh, L. 2016. VEGF receptor signal transduction–A brief update. Vascular pharmacology, 86: 14-17.


9. Cross, M. J., Dixelius, J., Matsumoto, T., Claesson-Welsh, L. 2003. VEGF-receptor signal transduction. Trends in biochemical sciences, 28(9): 488-494.


10. Czarkowska-Paczek, B., Zendzian-Piotrowska, M., Bartlomiejczyk, I., Przybylski, J., Gorski, J. 2010. Skeletal and heart muscle expression of PDGF-AA and VEGF-A after an acute bout of exercise and endurance training in rats. Medical Science Monitor, 16(5): BR147-BR153.


11. Doustar, Y. 2011. Effect of grape seed extract on cardiomyocyte apoptosis in streptozotocin induced diabetic rats. Medical Science Journal of Islamic Azad Univesity-Tehran Medical Branch, 21(3); 168-174.


12. Erekat, N.S., Al-Jarrah, M.D., Al Khatib, A.J. 2014. Treadmill exercise training improves vascular endothelial growth factor expression in the cardiac muscle of type I diabetic rats. Cardiology Research, 5(1): 23.


13. Farinha, J.B., Krause, M., Rodrigues-Krause, J., Reischak-Oliveira, A. 2017. Exercise for type 1 diabetes mellitus management: general considerations and new directions. Medical Hypotheses, 104: 147-153.


14. Garekani, E.T., Mohebbi, H., Kraemer, R.R., Fathi, R. 2011. Exercise training intensity/volume affects plasma and tissue adiponectin concentrations in the male rat. Peptides, 32(5): 1008-1012.


15. Ghahramani, M., Karbalaeifar, S. 2019. The Effect of Interval Training on Cardiac Angiogenesis Capacity in Rats with Myocardial Infarction. Report of Health Care, 5(1): 9-16.


16. Griffin, L. E., Witrick, K. A., Klotz, C., Dorenkott, M.R., Goodrich, K.M., Fundaro, G., Neilson, A.P. 2017. Alterations to metabolically active bacteria in the mucosa of the small intestine predict anti-obesity and anti-diabetic activities of grape seed extract in mice. Food and Function, 8(10): 3510-3522.


17. Huang, S., Yang, N., Liu, Y., Gao, J., Huang, T., Hu, L., Zhang, X. 2012. Grape seed proanthocyanidins inhibit colon cancer-induced angiogenesis through suppressing the expression of VEGF and Ang1. International journal of molecular medicine, 30(6): 1410-1416.


18. Iemitsu, M., Maeda, S., Jesmin, S., Otsuki, T., Miyauchi, T. 2006. Exercise training improves aging-induced downregulation of VEGF angiogenic signaling cascade in hearts. American Journal of Physiology-heart and Circulatory Physiology, 291(3): H1290-H1298.


19. Jashni, H. K., Mohebbi, H., Delpasand, A., Jahromy, H. K. 2015. Caloric restriction and exercise training, combined, not solely improve total plasma adiponectin and glucose homeostasis in streptozocin-induced diabetic rats. Sport sciences for health, 11(1): 81-86.


20. Jesmin, S., Zaedi, S., Shimojo, N., Iemitsu, M., Masuzawa, K., Yamaguchi, N., Miyauchi, T. 2007. Endothelin antagonism normalizes VEGF signaling and cardiac function in STZ-induced diabetic rat hearts. American Journal of Physiology-Endocrinology and Metabolism, 292(4): E1030-E1040.


21. Khazaei, M., Fallahzadeh, A.R., Sharifi, M.R., Afsharmoghaddam, N., Javanmard, S.H., Salehi, E. 2011. Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats. Clinics, 66(8): 1419-1424.


22. Melincovici, C.S., Boşca, A.B., Şuşman, S., Mărginean, M., Mihu, C., Istrate, M., Mihu, C.M. 2018. Vascular endothelial growth factor (VEGF)-key factor in normal and pathological angiogenesis. Rom Journal of Morphology and Embryology, 59(2): 455-467.


23. Melly, L.F., Marsano, A., Frobert, A., Boccardo, S., Helmrich, U., Heberer, M., Tevaearai, H.T. 2012. Controlled angiogenesis in the heart by cell-based expression of specific vascular endothelial growth factor levels. Human Gene Therapy, Part B: Methods, 23(5): 346-356.


24. Nagy, J.A., Dvorak, A.M., Dvorak, H.F. 2007. VEGF-A and the induction of pathological angiogenesis. Annual Review of Pathology: Mechanisms of Disease, 2: 251-275.


25. Olfert, I. M., Baum, O., Hellsten, Y., Egginton, S. 2016. Advances and challenges in skeletal muscle angiogenesis. American Journal of Physiology-Heart and Circulatory Physiology, 310(3): H326-H336.


26. Shah, B.N., Seth A. 2009. Textbook of Pharmacognosy and Phytochemistry. 1st Edition, Elsevier India, 586 p.


27. Shen, M., Yu, M., Qiu, C., Zhang, G., Li, J., Fang, W., Wang, Q. 2021. Myocardial angiogenesis induced by exercise training involves a regulatory mechanism mediated by kinin receptors. Clinical and Experimental Hypertension, 43(5): 408-415.


28. Shiojima, I., Sato, K., Izumiya, Y., Schiekofer, S., Ito, M., Liao, R., Walsh, K. 2005. Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. The Journal of Clinical Investigation, 115(8): 2108-2118.


29. Suzuki, J. 2005. Microvascular angioadaptation after endurance training with l‐arginine supplementation in rat heart and hindleg muscles. Experimental Physiology, 90(5): 763-771.


30. Tahergorabi, Z., Khazaei, M. 2012. Imbalance of angiogenesis in diabetic complications: the mechanisms. International Journal of Preventive Medicine, 3(12): 827.


31. Takahashi, H., Shibuya, M. 2005. The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clinical Science, 109(3): 227-241.


32. Umpierre, D., Ribeiro, P.A., Kramer, C.K., Leitão, C.B., Zucatti, A.T., Azevedo, M.J., Schaan, B.D. 2011. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. Jama, 305(17): 1790-1799.


33. Vali Zadeh, S., Motamedi, P., Karami, H., Rajabi, H. 2018. The effects of endurance training on gene expression of VEGF and VEGFR2 of cardiac tissue in Type 2 diabetic male wistar. Journal of Arak University of Medical Sciences, 21(6): 107-118.


34. Wen, W., Lu, J., Zhang, K., Chen, S. 2008. Grape seed extract inhibits angiogenesis via suppression of the vascular endothelial growth factor receptor signaling pathway. Cancer Prevention Research, 1(7): 554-561.


35. Zhao, T., Zhao, W., Chen, Y., Ahokas, R.A., Sun, Y. 2010. Vascular endothelial growth factor (VEGF)-A: role on cardiac angiogenesis following myocardial infarction. Microvascular Research, 80(2): 188-194.


36. Zheng, Y.-B., Meng, Q.-W., Zhao, W., Liu, B., Huang, J.-W., He, X., Lu, L.-G. 2014. Prognostic value of serum vascular endothelial growth factor receptor 2 response in patients with hepatocellular carcinoma undergoing transarterial chemoembolization. Medical Oncology, 31(3): 843.