نوع مقاله : مقاله پژوهشی Released under CC BY-NC 4.0 license I Open Access I
نویسندگان
1 گروه فیزیولوژی ورزشی، واحد ساری، دانشگاه آزاد اسلامی، ساری، ایران.
2 مرکز تحقیقات قلب و عروق، دانشگاه علوم پزشکی مازندران، ساری، ایران.
چکیده
مقدمه: کاردیومیوپاتی دیابتی خطر نارسایی قلب را افزایش می‌دهد. پیش‌آماده‌سازی ایسکمی یک اثر محافظتی در مقابل آسیب میوکارد دارد. هدف از تحقیق حاضر، بررسی اثر تمرین هوازی و دوزهای مختلف پیش‌آماده‌سازی ایسکمی در حجم‌های عضلانی مختلف بر بیان ژن NLRP3 و LC3 قلب رتهای ویستار دیابتی بود.
روش پژوهش: 35 رت نژاد ویستار به‌صورت تصادفی به هفت گروه: سالم، دیابتی، ایسکمی یک پا، ایسکمی دو پا، تمرین هوازی، تمرین+ایسکمی یک پا، دیابتی تمرین+ایسکمی دو پا تقسیم شدند. القای دیابت با تزریق یک‌مرحله‌ای STZ (دوز mg/kg 50) صورت گرفت. پیش‌آماده‌سازی ایسکمی شامل سه دور پنج‌دقیقه‌ای ایسکمی و پنج دقیقه جریان مجدد متعاقب بود. تمرین هوازی به مدت شش هفته و شامل دویدن روی نوار گردان با سرعت 9 متر در دقیقه و مدت 15 دقیقه در هفتۀ اول بود که در هفتۀ ششم به سرعت 18 متر در دقیقه و مدت 30 دقیقه رسید. بیان ژن NLRP3 و LC3 با روش real-time PCR اندازه‌گیری شد. از روش آماری واریانس یکطرفه و آزمون تعقیبی توکی استفاده شد.
یافته‌ها: دیابت با افزایش بیان NLRP3 و کاهش LC3 قلب نسبت به گروه سالم همراه بود (0001/0P=). متغیرهای پژوهش به‌ترتیب کاهش و افزایش معناداری در ایسکمی یک پا (021/0P=،0001/0P=)، ایسکمی دو پا (003/0P=،0001/0P=)، تمرین (005/0P= ،0001/0P=)، تمرین+ایسکمی یک پا (0001/0P=) و تمرین+ایسکمی دو پا (0001/0P=) نسبت به گروه دیابت داشت.
نتیجه‌گیری: به‌نظر می‌رسد که اثر پیش‌آماده‌سازی ایسکمی در کاهش NLRP3 و افزایش LC3 قلب رتهای دیابتی مستقل از حجم عضلانی درگیر ایسکمی است و تمرین هوازی به‌همراه پیش‌آماده‌سازی ایسکمی اثر بیشتری دارد.
کلیدواژه‌ها
موضوعات
عنوان مقاله [English]
Response of Myocardial NLRP3 and LC3 Gene Expression in Male Diabetic Rats to Ischemic Preconditioning with Different Muscle Masses and Aerobic Training
نویسندگان [English]
- Fazeleh Akbarnia 1
- Amin Farzaneh 1
- abdollah Hashemvarzi 1
- Ali SGHAR Farsavian 2
1 Department of Exercise Physiology, Sar.C., Islamic Azad University, Sari, Iran.
2 Department of Cardiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
چکیده [English]
Introduction: Diabetic cardiomyopathy increases the risk of heart failure. Ischemic preconditioning (IPC) has a protective effect against myocardial injury. The present study aimed to investigate the effect of aerobic training and IPC with different muscle masses on myocardial NLRP3 and LC3 gene expression in diabetic Wistar rats.
Methods: Thirty-five Wistar rats were randomly divided into seven groups: Healthy control (C), diabetic (D), one-leg ischemia (1IP), two-legs ischemia (2IP), aerobic training (T), one-leg ischemia+aerobic training (1IPT), two-legs ischemia+aerobic training (2IPT). Diabetes was induced by a single injection of STZ (50 mg/kg). IPC consisted of three cycles of 5-minute ischemia followed by 5 minutes of reperfusion. Aerobic training was performed on a treadmill for six weeks, starting at 9 m/min for 15 minutes in the first week and gradually increasing to 18 m/min for 30 minutes by the sixth week. Myocardial NLRP3 and LC3 gene expression levels were measured using real-time PCR. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test.
Results: NLRP3 Gene expression significantly increased, and LC3 decreased in D compared to C (p=0.0001). NLRP3 and LC3 decreased and increased significantly, respectively, in 1IP (p=0.0001,p=0.021), 2IP (p=0.0001,p=0.003), T (p=0.0001, p=0.005), 1IPT (p=0.0001) and 2IPT (p=0.0001) compared to the C.
Conclusion: It appears that the effect of ischemic preconditioning on reducing cardiac NLRP3 and increasing LC3 in diabetic rats is independent of the mass of ischemic muscle involved. Aerobic training with IPC is more effective in improving NLRP3 and LC3 in diabetes.
کلیدواژه‌ها [English]
- Inflammation
- Ischemic preconditioning
- Exercise training
- Cardiomyopathy
- Wistar rats
- Tan Y, Zhang Z, Zheng C, Wintergerst KA, Keller BB, Cai L. Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence. Nature Reviews Cardiology. 2020;17(9):585-607. doi: 10.1038/s41569-020-0339-2.
- Nishida K, Otsu K. Inflammation and metabolic cardiomyopathy. Cardiovascular research. 2017;113(4):389-98. doi: 10.1093/cvr/cvx012.
- Jia G, Hill MA, Sowers JR. Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circulation research. 2018;122(4):624-38. doi: 10.1161/CIRCRESAHA.117.311586.
- Mangan MS, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E. Targeting the NLRP3 inflammasome in inflammatory diseases. Nature reviews Drug discovery. 2018;17(8):588-606. https://doi.org/10.1038/nrd.2018.97
- Sharma BR, Kanneganti T-D. NLRP3 inflammasome in cancer and metabolic diseases. Nature immunology. 2021;22(5):550-9. https://doi.org/10.1038/s41590-021-00886-5
- Toldo S, Mezzaroma E, Buckley LF, Potere N, Di Nisio M, Biondi-Zoccai G, et al. Targeting the NLRP3 inflammasome in cardiovascular diseases. Pharmacology & therapeutics. 2022;236:108053. doi: 10.1016/j.pharmthera.2021.108053.
- Mao S, Chen P, Pan W, Gao L, Zhang M. Exacerbated post‐infarct pathological myocardial remodelling in diabetes is associated with impaired autophagy and aggravated NLRP3 inflammasome activation. ESC Heart Failure. 2022;9(1):303-17. doi: 10.1002/ehf2.13754.
- Lu Q-B, Ding Y, Liu Y, Wang Z-C, Wu Y-J, Niu K-M, et al. Metrnl ameliorates diabetic cardiomyopathy via inactivation of cGAS/STING signaling dependent on LKB1/AMPK/ULK1-mediated autophagy. Journal of Advanced Research. 2023;51:161-79. doi: 10.1016/j.jare.2022.10.014.
- Wang H, Wang L, Hu F, Wang P, Xie Y, Li F, et al. Neuregulin-4 attenuates diabetic cardiomyopathy by regulating autophagy via the AMPK/mTOR signalling pathway. Cardiovascular Diabetology. 2022;21(1):205. doi: 10.1186/s12933-022-01643-0.
- Kanamori H, Takemura G, Goto K, Tsujimoto A, Mikami A, Ogino A, et al. Autophagic adaptations in diabetic cardiomyopathy differ between type 1 and type 2 diabetes. Autophagy. 2015;11(7):1146-60. doi: 10.1080/15548627.2015.1051295.
- Munasinghe PE, Riu F, Dixit P, Edamatsu M, Saxena P, Hamer NS, et al. Type-2 diabetes increases autophagy in the human heart through promotion of Beclin-1 mediated pathway. International journal of cardiology. 2016;202:13-20. doi: 10.1016/j.ijcard.2015.08.111
- Kar S, Shahshahan HR, Hackfort BT, Yadav SK, Yadav R, Kambis TN, et al. Exercise training promotes cardiac hydrogen sulfide biosynthesis and mitigates pyroptosis to prevent high-fat diet-induced diabetic cardiomyopathy. Antioxidants. 2019;8(12):638. doi: 10.3390/antiox8120638.
- Vandanmagsar B, Youm Y-H, Ravussin A, Galgani JE, Stadler K, Mynatt RL, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature medicine. 2011;17(2):179-88. doi: 10.1038/nm.2279.
- Quiroga R, Nistal E, Estébanez B, Porras D, Juárez-Fernández M, Martínez-Flórez S, et al. Exercise training modulates the gut microbiota profile and impairs inflammatory signaling pathways in obese children. Experimental & molecular medicine. 2020;52(7):1048-61. doi: 10.1038/s12276-020-0459-0.
- Chen X, Li H, Wang K, Liang X, Wang W, Hu X, et al. Aerobic exercise ameliorates myocardial inflammation, fibrosis and apoptosis in high-fat-diet rats by inhibiting P2X7 purinergic receptors. Frontiers in physiology. 2019;10:1286. doi: 10.3389/fphys.2019.01286.
- Zaidi H, Byrkjeland R, Njerve IU, Åkra S, Solheim S, Arnesen H, et al. Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients with combined coronary artery disease and type 2 diabetes mellitus: Sub-study of a randomized control trial. Diabetes and Vascular Disease Research. 2019;16(4):360-8. doi: 10.1177/1479164119836922.
- Zare Damirchi Z, Narimani Rad M, Hadi H. The effect of eight weeks of endurance training and olive oil supplementation on IL-1ß and NLRP3 indices in obese male rats. Yafteh. 2020;22(3). Available from: https://sid.ir/paper/367409/en (In Persian)
- Grumati P, Coletto L, Schiavinato A, Castagnaro S, Bertaggia E, Sandri M, et al. Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles. Autophagy. 2011;7(12):1415-23. doi: 10.4161/auto.7.12.17877.
- Jafari A, Zarghami Khameneh A, Nikookheslat S, Karimi P, Pashaei Z. Effects of Two Months of High Intensity Interval Training and Caffeine Supplementation on the Expression of Beclin-1 and Bcl-2 Proteins in the Myocardium of Type 2 Male Diabetic Rats. Journal of Applied Health Studies in Sport Physiology. 2021;8(2):83-91. doi: 10.22049/jahssp.2022.27500.1401. (In Persian)
- Daneshyar S, Tavoosidana G, Bahmani M, Basir SS, Delfan M, Laher I, et al. Combined effects of high fat diet and exercise on autophagy in white adipose tissue of mice. Life Sciences. 2023;314:121335. doi: 10.1016/j.lfs.2022.121335.
- O'Brien L, Jacobs I. Methodological variations contributing to heterogenous ergogenic responses to ischemic preconditioning. Frontiers in physiology. 2021;12:656980. doi:10.3389/fphys.2021.656980
- Lang JA, Kim J. Remote ischaemic preconditioning–translating cardiovascular benefits to humans. The Journal of Physiology. 2022;600(13):3053-67. doi: 10.1113/JP282568.
- Jones H, Nyakayiru J, Bailey TG, Green DJ, Cable NT, Sprung VS, et al. Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males. European journal of preventive cardiology. 2015;22(8):1083-7. doi: 10.1177/2047487314547657
- Maxwell JD, Carter HH, Hellsten Y, Miller GD, Sprung VS, Cuthbertson DJ, et al. Seven-day remote ischaemic preconditioning improves endothelial function in patients with type 2 diabetes mellitus: a randomised pilot study. European Journal of Endocrinology. 2019;181(6):659-69. doi: 10.1530/EJE-19-0378.
- Charan K, Goyal A, Gupta JK, Yadav HN. Role of atrial natriuretic peptide in ischemic preconditioning–induced cardioprotection in the diabetic rat heart. Journal of Surgical Research. 2016;201(2):272-8. doi: 10.1016/j.jss.2015.10.045.
- Leurcharusmee P, Sawaddiruk P, Punjasawadwong Y, Sugandhavesa N, Klunklin K, Tongprasert S, et al. Ischemic preconditioning upregulates Mitofusin2 and preserves muscle strength in tourniquet-induced ischemia/reperfusion. Journal of orthopaedic translation. 2022;35:113-21. doi: 10.1016/j.jot.2022.09.012.
- Akbarnia F, Farzaneh Hesari A, Hashemvarzi A, Farsavian A. The effect of endurance training and remote ischemic preconditioning on myocardial Beclin-1 gene expression in diabetic rats. Daneshvar Medicine. 2025;32(5):34-43. doi: 10.22070/daneshmed.2024.19695.1554. (In Persian)
- Arabzadeh E, Samadian Z, Tofighi A, Tolouei Azar J. Alteration of follistatin-like 1, neuron-derived neurotrophic factor, and vascular endothelial growth factor in diabetic cardiac muscle after moderate-intensity aerobic exercise with insulin. Sport sciences for health. 2020;16(3):491-9. doi:10.1007/s11332-020-00631-9
- Zhang L, Liu H-H, Li F, Yang F, Qian L-L, Wang R-X. The role of nlrp3 inflammasome signaling on arrhythmias in diabetes. Journal of Inflammation Research. 2022:6883-9. doi: 10.2147/JIR.S390310
- Bai Y, Mu Q, Bao X, Zuo J, Fang X, Hua J, et al. Targeting NLRP3 inflammasome in the treatment of diabetes and diabetic complications: Role of natural compounds from herbal medicine. Aging and disease. 2021;12(7):1587. doi:10.14336/AD.2021.0318.
- Hu S, Hu Y, Long P, Li P, Chen P, Wang X. The effect of tai chi intervention on NLRP3 and its related antiviral inflammatory factors in the serum of patients with pre-diabetes. Frontiers in Immunology. 2022;13:1026509. doi: 10.3389/fimmu.2022.1026509.
- Fatemi SA, Hesari AF, Shahamat MD. NLRP-3 Expression in Pancreatic Tissue Following Moderate and High Intensity Interval Training with Liposomal Alpha-Lipoic Acid Supplement in Diabetic Rats. Journal of Shahid Sadoughi University of Medical Sciences. 2022. http://jssu.ssu.ac.ir/article-1-5517-en.html. (In Persian)
- Khodaei O, Bolboli L, Siakkohian M, Bagaei B. The effect of 8-weeks of high intensity interval training (HIIT) along with L-cysteine consumption on the level of NLRP3 in the heart tissue of rats with type 2 diabetes. Journal of Applied Health Studies in Sport Physiology. 2024. doi: 10.22049/jahssp.2024.29872.1671 (In Persian)
- Wen R-M, Lyu H-Y, Chang B, Yi X-J. Role of NLRP3 inflammasome in diabetes mellitus and exercise intervention. Sheng li xue bao:[Acta Physiologica Sinica]. 2023;75(6):788-98. PMID: 38151344.
- Ma M, Chen W, Hua Y, Jia H, Song Y, Wang Y. Aerobic exercise ameliorates cardiac hypertrophy by regulating mitochondrial quality control and endoplasmic reticulum stress through M2AChR. Journal of Cellular Physiology. 2021;236(9):6581-96. doi: 10.1002/jcp.30342.
- Sun Y, Ding S. NLRP3 inflammasome in diabetic cardiomyopathy and exercise intervention. International Journal of Molecular Sciences. 2021;22(24):13228. doi: 10.3390/ijms222413228.
- Zhang J, Huang L, Shi X, Yang L, Hua F, Ma J, et al. Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK/NLRP3 inflammasome pathway. Aging (Albany NY). 2020;12(23):24270. doi: 10.18632/aging.202143.
- Luo N, Liu J, Chen Y, Li H, Hu Z, Abbott GW. Remote ischemic preconditioning STAT3-dependently ameliorates pulmonary ischemia/reperfusion injury. PloS one. 2018;13(5):e0196186. doi: 10.1371/journal.pone.0196186.
- Ginis I, Jaiswal R, Klimanis D, Liu J, Greenspon J, Hallenbeck JM. TNF-α–induced tolerance to ischemic injury involves differential control of NF-κB transactivation: the role of NF-κB association with p300 adaptor. Journal of Cerebral Blood Flow & Metabolism. 2002;22(2):142-52. doi: 10.1097/00004647-200202000-00002
- Yang G, Yang Y, Li Y, Hu Z. Remote liver ischaemic preconditioning protects rat brain against cerebral ischaemia–reperfusion injury by activation of an AKT‐dependent pathway. Experimental physiology. 2020;105(5):852-63. doi: 10.1113/EP088394. Epub 2020 Apr 3.
- Liu X, Chen H, Yan Z, Du L, Huang D, Gao WD, et al. Remote liver ischemic preconditioning attenuates myocardial ischemia/reperfusion injury in streptozotocin-induced diabetic rats. Scientific reports. 2021;11(1):1903. doi: 10.1038/s41598-021-81422-1
- Sadeghi S, Delphan M, Shams M, Esmaeili F, Shanaki-Bavarsad M, Shanaki M. The high-intensity interval training (HIIT) and curcumin supplementation can positively regulate the autophagy pathway in myocardial cells of STZ-induced diabetic rats. BMC Research Notes. 2023;16(1):21. doi: 10.1186/s13104-023-06295-1
- Zhang L, Ding W-y, Wang Z-h, Tang M-x, Wang F, Li Y, et al. Early administration of trimetazidine attenuates diabetic cardiomyopathy in rats by alleviating fibrosis, reducing apoptosis and enhancing autophagy. Journal of translational medicine. 2016;14(1):109. doi: 10.1186/s12967-016-0849-1.
- Golpasandi H, Rahimi MR, Ahmadi S. Investigating the mutual effects of autophagy and apoptosis in heart tissue of type 2 diabetic rats in interaction with aerobic exercise training and vitamin D3 injection. Journal of Sport and Exercise Physiology. 2024;17(2):34-47. doi: 10.48308/joeppa.2024.235803.1257 (In Persian)
- Zanganeh F, Farzanegi P, Asgharpour H. Effect of Exercise Training and Atorvastatin Supplementation on Beclin1, LC3-I and LC3-П Expression in Old Diabetic Rats. Medical Laboratory Journal. 2022;16(1). https://sid.ir/paper/1014522/en
- Hashemi Chashmi SZ, Souri H, Jalali Dehkordi K. Effects of 8 weeks of continuous and intermittent aerobic training with resveratrol supplementation on Beclin-1 and LC3I-II genes expression in heart tissue of diabetic male rats. Journal of Applied Health Studies in Sport Physiology. 2021;8(2):61-9. (In Persian)
- Liu Y-Y, Sun C, Xue F-S, Yang G-Z, Li H-X, Liu Q, et al. Effect of autophagy inhibition on the protection of ischemia preconditioning against myocardial ischemia/reperfusion injury in diabetic rats. Chinese Medical Journal. 2018;131(14):1702-9. doi: 10.4103/0366-6999.235867.
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