تأثیر دو نوع تمرین (تداومی و تناوبی) و داروی آترواستاتین بر بیان ژن‌های PP2Ac و GSK-3β بافت قلب رت‌های مدل دیابتی
محورهای موضوعی :
مجله پلاسما و نشانگرهای زیستی
مریم ابراهیمی
1
,
حبیب اصغرپور
2
,
پروین فرزانگی
3
,
رضا رضایی شیرازی
4
1 - گروه فیزیولوژی ورزشی، واحد علی آباد کتول، دانشگاه آزاد اسلامی، علی آباد کتول، ایران
2 - استادیار گروه فیزیولوژی ورزشی دانشکده تربیت بدنی و علوم ورزشی دانشگاه آزاد اسلامی واحد علی آباد
3 - دانشیار، گروه فیزیولوژی ورزشی، واحد ساری، دانشگاه آزاد اسلامی، ساری، ایران
4 - استادیار، گروه تربیت‌بدنی و علوم‌ورزشی واحد علی‌آباد کتول، دانشگاه آزاد اسلامی، علی‌آباد کتول، ایران
تاریخ دریافت : 1401/06/03
تاریخ پذیرش : 1401/12/18
تاریخ انتشار : 1402/05/01
کلید واژه:
کاردیومیوپاتی دیابت,
GSK-3β,
آترواستاتین,
PP2Ac,
تمرینات تداومی و تناوبی,
چکیده مقاله :
زمینه و هدف: به غیر از فشارخون بالا و بیماری عروق کرونر دیابت نیز می تواند به طور مستقیم بر ساختار و عملکرد قلب تأثیر گذارد و عارضه ای را که کاردیومیوپاتی دیابتی نام گرفته است به دنبال داشته باشد، هدف از پژوهش حاضر بررسی اثر دو نوع تمرین (تداومی و تناوبی) و داروی آترواستاتین بر بیان ژن های PP2Ac و GSK-3β بافت قلب رت های مدل دیابتی می باشد.مواد و روش: 64 سر موش صحرایی نر، که در 8 گروه به صورت تصادفی تقسیم بندی شدند: شامل 1) کنترل، 2) دیابتی، 3) دیابتی+ تداومی، 4) دیابتی + تناوبی، 5) آترواستاتین، 6) تداومی + آترواستاتین، 7) تناوبی + آترواستاتین و 8)سالین. رت ها دو نوع تمرین تداومی و تناوبی را 5 روز در هفته و به مدت 8 هفته اجرا نمودند. آترواستاتین به صورت روزانه با دوز 20 میلی گرم به ازای هر کیلوگرم وزن بدن به صورت درون صفاقی به آنان تزریق شد.نتایج: القای دیابت منجر به کاهش معنی دار بیان ژن PP2Ac و افزایش معنی دار بیان ژن GSK-3β بافت قلب رت ها شد، که انجام تمرین تداومی و ترکیب تمرین تناوبی و تداومی با داروی آترواستاتین منجر به افزایش PP2Ac و کاهش GSK-3β بافت قلب رت های دیابتی نسبت به گروه کنترل دیابتی گردید.نتیجه گیری: این احتمال وجود دارد که فعالیت ورزشی منظم در ترکیب با آترواستاتین ب تواند از طریق افزایش ژن PP2Ac و کاهش ژن GSK-3β بافت قلب از توسعه کاردیومیوپاتی که در اثر القای دیابت بوجود آمد جلوگیری نماید و دارای اثر حفاظتی بر قلب باشد.
چکیده انگلیسی:
Background and Aim: Apart from high blood pressure and coronary artery disease, diabetes can directly affect the structure and function of the heart and lead to a complication called diabetic cardiomyopathy. The purpose of this study is to investigate the effect of two types of training and the drug atrostatin on the expression of PP2Ac and GSK-3β genes in the heart tissue of diabetic model rats.Methods and Materials: 64 male rats, which were randomly divided into 8 groups: including 1) control, 2) diabetic, 3) diabetic + persistent, 4) Diabetic + periodic, 5) atherostatin, 6) continuous + atrostatin, 7) periodic + atrostatin and 8) saline. The rats of the exercise groups performed two types of continuous and intermittent exercise 5 days a week for 8 weeks. Atrostatin was injected intraperitoneally daily at a dose of 20 mg per kg body weight.Results: Induction of diabetes led to a decrease in the expression of the PP2Ac gene and an increase in the expression of the GSK-3β gene in the heart tissue, and continuous exercise and the combination of intermittent and continuous exercise with the drug atrostatin led to an increase in PP2Ac and a decrease in GSK-3β in the heart tissue of diabetic rats compared to the diabetic group.Conclusion: It is possible that regular exercise in combination with atrostatin can prevent the development of diabetes-induced cardiomyopathy by increasing the PP2Ac gene and decreasing the GSK-3β gene in the heart tissue which has a protective effect on the heart of diabetic rats.
منابع و مأخذ:
Alex Cleber Improta-Caria, Ricardo Augusto Leoni De Sousa, Leonardo Roever, Tiago Fernandes, Edilamar Menezes de Oliveira, Roque Aras Júnior, Bruno Solano de Freitas Souza. MicroRNAs in type 2 diabetes mellitus: potential role of physical exercise. Rev. Cardiovasc. Med. 2022; 23(1): 029.
Jokar M, Sherafati Moghadam2 M, Salesi M. The effect of endurance exercise on the content of AMPK and PGC-1α proteins in the left ventricular heart tissue of male rats with type2 diabetes. Iranian Journal of Diabetes and Metabolism; Vol. 19, No 5, 2020. [In persion].
Hölscher M, Bode C, Bugger H. Diabetic cardiomyopathy: does the type of diabetes matter?. International journal of molecular sciences 2016;17(12):1-10.
Kim JA, Jang HJ, Martinez-Lemus LA, Sowers JR. Activation of mTOR/p70S6 kinaseby ANG II inhibits insulin-stimulated endothelial nitric oxide synthase and vasodilation. American Journal of Physiology-Endocrinology and Metabolism2011;302(2):201-8.
Jia G, Hill MA and Sowers JR. Diabetic Cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ. Res. 2018. 122 624–638.
Jia G, DeMarco VG, Sowers JR. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nature Reviews Endocrinology 2016;12(3):144-53.
Nizamutdinova IT, Guleria RS, Singh AB, Kendall JA Jr., Baker KM, Pan J. Retinoic acid protects cardiomyocytes from high glucose-induced apoptosis through inhibition of NF-kappaB signaling pathway. J Cell Physiol. 2013; 228(2):380±392.
Yao XQ, Zhang XX, Yin YY, Liu B, Luo DJ, Liu D, et al. Glycogen synthase kinase-3beta regulates Tyr307 phosphorylation of protein phosphatase-2A via protein tyrosine phosphatase 1B but not Src. Biochem J. 2011; 437(2):335±344.
Hanqing Zeng, Zhongtao Liu. Atorvastatin Induces Hepatotoxicity in Diabetic Rats via Oxidative Stress, Inflammation, and Anti-Apoptotic Pathway. Med Sci Monit, 2019; 25: 6165-6173.
Levadot J, Asahara T. Effects of statins on angiogenesis and vasculogenesis. Rev Esp Cardiol. 2012;55:838-44.
Abdel-Hamid AA, Firgany A. Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress. J Mol Histol. 2015; 46(4±5):337±345.
Jin Y, Sui HJ, Dong Y, Ding Q, Qu WH, Yu SX, et al. Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3beta signaling pathways. Acta Pharmacol 2012; 33(7):861±872.
Improta-Caria AC, Aras R. Treinamento com Exercício Físicoe Doença de Chagas: Função Potencial dos MicroRNAs. Arquivos Brasileiros De Cardiologia. 2021; 117: 132–141.
Shawn Yongshun Wang, Siyu Zhu4 & Jian Wu, Maomao Zhang, Yousheng Xu, Wei Xu et al. Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy. Journal of Molecular Medicine. 2020. 10.1007/s00109-019-01861-2.
Seo DY et al. Aged garlic extract enhances exercise-mediated improvement of metabolic parameters in high fat diet-induced obese rats. Nutr Res Pract. 2012. 6(6):513–519
Seo DY, Lee SR, Kim N, Ko KS, Rhee BD, Han J. Agerelated changes in skeletal muscle mitochondria: the role of exercise. Integr Med Res. 2016. 5(3):182–186
Oyenihi AB, Ayeleso AO, Mukwevho E, Masola B. Antioxidant
strategies in the management of diabetic neuropathy. Biomed Res Int 2015; 2015: 515042.
Chen SL, Hu ZY, Zuo GF, Li MH, Li B. I(f) current channel inhibitor (ivabradine) deserves cardioprotective effect via down-regulating the expression of matrix metalloproteinase (MMP)-2 and attenuating apoptosis in diabetic mice. BMC Cardiovasc Disord. 2014; 14:150.
Kempuraj D, Thangavel R, Natteru PA, Selvakumar GP, Saeed D, Zahoor H, et al. Neuroinflammation induces neurodegeneration. J Neurol Neurosurg Spine 2016; 1: 1003.
Cheng G, Li L. High-glucose-induced apoptosis, ROS production and pro-inflammatory response in cardiomyocytes is attenuated by metformin treatment via PP2A activation. J Biosci (2020) 45:126.
Enjoji S and Ohama T. The role of protein phosphatase 2A in inflammation and cancer. Nihon Yakurigaku Zasshi. 2017. 149 208–212.
Nakajima S and Kitamura M. Bidirectional regulation of NF-jB by reactive oxygen species: a role of unfolded protein response. Free Radic. Biol. Med. 2013. 65 162–174.
Mehrad H, Mokhtari-Dizaji M, Ghanaati H. Effect of high-dose atorvastatin on advanced soft atherosclerotic plaque in rabbit carotid artery using ultrasonographic and histological methods. Feyz 2014; 18(1): 9-22
Ren X-m, Zuo G-f, Wu W, Luo J, Ye P, Chen S-l, et al. Atorvastatin Alleviates Experimental Diabetic Cardiomyopathy by Regulating the GSK-3β-PP2Ac-NF-κB Signaling Axis. PLoS ONE. 2016. 11(11): e0166740
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Alex Cleber Improta-Caria, Ricardo Augusto Leoni De Sousa, Leonardo Roever, Tiago Fernandes, Edilamar Menezes de Oliveira, Roque Aras Júnior, Bruno Solano de Freitas Souza. MicroRNAs in type 2 diabetes mellitus: potential role of physical exercise. Rev. Cardiovasc. Med. 2022; 23(1): 029.
Jokar M, Sherafati Moghadam2 M, Salesi M. The effect of endurance exercise on the content of AMPK and PGC-1α proteins in the left ventricular heart tissue of male rats with type2 diabetes. Iranian Journal of Diabetes and Metabolism; Vol. 19, No 5, 2020. [In persion].
Hölscher M, Bode C, Bugger H. Diabetic cardiomyopathy: does the type of diabetes matter?. International journal of molecular sciences 2016;17(12):1-10.
Kim JA, Jang HJ, Martinez-Lemus LA, Sowers JR. Activation of mTOR/p70S6 kinaseby ANG II inhibits insulin-stimulated endothelial nitric oxide synthase and vasodilation. American Journal of Physiology-Endocrinology and Metabolism2011;302(2):201-8.
Jia G, Hill MA and Sowers JR. Diabetic Cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ. Res. 2018. 122 624–638.
Jia G, DeMarco VG, Sowers JR. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nature Reviews Endocrinology 2016;12(3):144-53.
Nizamutdinova IT, Guleria RS, Singh AB, Kendall JA Jr., Baker KM, Pan J. Retinoic acid protects cardiomyocytes from high glucose-induced apoptosis through inhibition of NF-kappaB signaling pathway. J Cell Physiol. 2013; 228(2):380±392.
Yao XQ, Zhang XX, Yin YY, Liu B, Luo DJ, Liu D, et al. Glycogen synthase kinase-3beta regulates Tyr307 phosphorylation of protein phosphatase-2A via protein tyrosine phosphatase 1B but not Src. Biochem J. 2011; 437(2):335±344.
Hanqing Zeng, Zhongtao Liu. Atorvastatin Induces Hepatotoxicity in Diabetic Rats via Oxidative Stress, Inflammation, and Anti-Apoptotic Pathway. Med Sci Monit, 2019; 25: 6165-6173.
Levadot J, Asahara T. Effects of statins on angiogenesis and vasculogenesis. Rev Esp Cardiol. 2012;55:838-44.
Abdel-Hamid AA, Firgany A. Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress. J Mol Histol. 2015; 46(4±5):337±345.
Jin Y, Sui HJ, Dong Y, Ding Q, Qu WH, Yu SX, et al. Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3beta signaling pathways. Acta Pharmacol 2012; 33(7):861±872.
Improta-Caria AC, Aras R. Treinamento com Exercício Físicoe Doença de Chagas: Função Potencial dos MicroRNAs. Arquivos Brasileiros De Cardiologia. 2021; 117: 132–141.
Shawn Yongshun Wang, Siyu Zhu4 & Jian Wu, Maomao Zhang, Yousheng Xu, Wei Xu et al. Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy. Journal of Molecular Medicine. 2020. 10.1007/s00109-019-01861-2.
Seo DY et al. Aged garlic extract enhances exercise-mediated improvement of metabolic parameters in high fat diet-induced obese rats. Nutr Res Pract. 2012. 6(6):513–519
Seo DY, Lee SR, Kim N, Ko KS, Rhee BD, Han J. Agerelated changes in skeletal muscle mitochondria: the role of exercise. Integr Med Res. 2016. 5(3):182–186
Oyenihi AB, Ayeleso AO, Mukwevho E, Masola B. Antioxidant
strategies in the management of diabetic neuropathy. Biomed Res Int 2015; 2015: 515042.
Chen SL, Hu ZY, Zuo GF, Li MH, Li B. I(f) current channel inhibitor (ivabradine) deserves cardioprotective effect via down-regulating the expression of matrix metalloproteinase (MMP)-2 and attenuating apoptosis in diabetic mice. BMC Cardiovasc Disord. 2014; 14:150.
Kempuraj D, Thangavel R, Natteru PA, Selvakumar GP, Saeed D, Zahoor H, et al. Neuroinflammation induces neurodegeneration. J Neurol Neurosurg Spine 2016; 1: 1003.
Cheng G, Li L. High-glucose-induced apoptosis, ROS production and pro-inflammatory response in cardiomyocytes is attenuated by metformin treatment via PP2A activation. J Biosci (2020) 45:126.
Enjoji S and Ohama T. The role of protein phosphatase 2A in inflammation and cancer. Nihon Yakurigaku Zasshi. 2017. 149 208–212.
Nakajima S and Kitamura M. Bidirectional regulation of NF-jB by reactive oxygen species: a role of unfolded protein response. Free Radic. Biol. Med. 2013. 65 162–174.
Mehrad H, Mokhtari-Dizaji M, Ghanaati H. Effect of high-dose atorvastatin on advanced soft atherosclerotic plaque in rabbit carotid artery using ultrasonographic and histological methods. Feyz 2014; 18(1): 9-22
Ren X-m, Zuo G-f, Wu W, Luo J, Ye P, Chen S-l, et al. Atorvastatin Alleviates Experimental Diabetic Cardiomyopathy by Regulating the GSK-3β-PP2Ac-NF-κB Signaling Axis. PLoS ONE. 2016. 11(11): e0166740
