臺灣博碩士論文加值系統

運動時造成的肌肉損傷會使身體進行發炎反應，生理上降低了肌肉收縮之效率進而降低運動表現，更有可能對日常生活造成不便。諸多研究顯示，白藜蘆醇對於肌肉損傷具有抗發炎與降低氧化壓力的功能；此外，補充白藜蘆醇亦被證實可以加速挫傷後的肌肉修復與運動表現(如：有氧運動與抓力)之恢復。然而，肌肉容易以離心收縮的狀態下造成損傷，由於白藜蘆醇對於離心收縮所造成的運動傷害是否具有相同生理效益上尚未有明確的定論。因此，本研究以離心收縮誘導肌肉損傷的小鼠動物模式，進一步探討白藜蘆醇對其抗發炎、抗氧化及能量代謝的影響，並觀察是否因白藜蘆醇補充達到改善運動表現；並利用RNA sequencing的方法，驗證肌肉中能量利用、抗發炎及抗氧化相關基因表現量是否有因為離心損傷運動與白藜蘆醇的增補而有所調節，並進一步探討白藜蘆醇可能的調節機轉。本實驗分為長期及短期下坡跑誘導小鼠離心損傷並介入白藜蘆醇，共分成四組，控制組(NC)、運動組(EX)、運動搭配低劑量白藜蘆醇組(EX+RES25)及運動搭配低劑量白藜蘆醇組(EX+RES150)。長期下坡跑力竭結果顯示，介入白藜蘆醇的兩組進行力竭跑的時間均顯著長於EX組；EX+RES150組之GLUT4 mRNA表現量顯著高於EX組，AMPK α1 mRNA表現量則是因為運動而使得EX組、EX+RES25組及EX+RES150組高於NC組。透過RNA sequencing發現長期介入白藜蘆醇後，相較於抗發炎及抗氧化，能量利用的效果較顯著。短期下坡跑力竭結果顯示，EX+RES150組跑的時間長於EX組；TNF-α mRNA表現量方面，EX+RES150組均比EX組低；能量利用的部分，EX+RES150組在不同肌肉中帶來的效果較EX+RES25組顯著。因此，透過本實驗得知長期及短期介入高劑量白藜蘆醇均可以提升運動中肌肉對能量的利用，而短期介入白藜蘆醇對發炎及氧化的效果較長期為佳。

Muscle damage caused by exercise can cause the body to carry out an inflammatory response, which physiologically reduces the efficiency of muscle contraction and thus reduces exercise performance and is more likely to cause inconvenience to daily life. Studies have shown that resveratrol has anti-inflammatory and anti-oxidative properties for muscle damage. In addition, resveratrol has also been shown to accelerate muscle repair and promote exercise performance after contusion (eg: aerobic exercise and grip strength) recovery. The one of muscle contraction, eccentric contraction, easily causes muscle damage. However, whether resveratrol has the same physiological benefits for sports injury caused by eccentric contraction remains unknown. Thus, we aim to further explore the effects of resveratrol on its anti-inflammatory, antioxidant, and energy metabolism, and to observe whether resveratrol could improve exercise performance by the model of eccentric contraction-induced muscle damage in this study. The experiment was divided into long-term and short-term and both intervened with resveratrol. Mice were divided into four groups: control group (NC), exercise group (EX), exercise combined with low-dose resveratrol group (EX+RES25) and exercise combined with high-dose resveratrol group (EX+RES150). The results of long-term downhill running in the exhausting test showed that the time of exhaustive running in the two groups with the intervention of resveratrol was significantly longer than that in the EX group. The mRNA expression level of GLUT4 in the EX+RES150 group was significantly higher than that in the EX group. The mRNA expression level of AMPK α1 was significantly higher in the EX+RES150 group than in the EX group. Through RNA sequencing, it was found that the effect of energy utilization was more significant than that of anti-inflammatory and anti-oxidation after long-term intervention of resveratrol. The results of short-term downhill running in the exhausting test showed that the running time of the EX+RES150 group was longer than that of the EX group. In terms of TNF-α mRNA expression, the EX+RES150 group was lower than the EX group. The energy utilization of the EX+RES150 group was more significant than that of the EX+RES25 group in different muscles. To sum up, those results showed that both long-term and short-term intervention with high-dose resveratrol can improve the utilization of energy, and short-term intervention of resveratrol has better effects on inflammation and oxidation than long-term.

目錄
中文摘要 i
Abstract ii
致謝 iii
目錄 v
圖目錄 x
表目錄 xiii
第一章 研究動機與目的 1
第二章 文獻回顧 2
第一節 運動健康促進與生理適應 2
一、國人運動比例 2
二、運動的好處 3
三、運動種類及傷害 3
四、運動肌肉發炎反應 4
五、運動氧化傷害 4
六、運動過程能量利用 5
第二節 酚類物質 6
一、多酚類 6
二、白藜蘆醇 6
第三節 酚類物質生理活性應用於運動生理之效益 7
一、抗氧化 7
二、抗發炎 7
三、能量利用 8
第四節 基因體學 9
第三章 實驗假說 11
一、介入白藜蘆醇減輕運動過程下發炎狀況 11
二、介入白藜蘆醇降低運動過程下肌肉中氧化壓力 11
三、介入白藜蘆醇提升運動表現 11
四、介入白藜蘆醇調控能量利用率 11
第四章 材料與方法 12
第一節 實驗動物 12
第二節 實驗分組 13
第三節 實驗流程 14
第四節 運動介入 17
一、適應跑及正式運動訓練(長期及短期) 17
二、力竭測試 17
第五節 樣本採集 18
一、血液樣本 18
二、臟器樣本採集 18
第六節 生化分析 19
一、血液分析 19
第七節 功能性基因表現與基因體分析 19
一、即時聚合酶連鎖反應 19
二、RNA sequencing 20
1. 實驗流程 20
2. 定序流程 21
第七節 統計分析 23
第五章 實驗結果 24
第一節 長期下坡跑實驗結果 24
一、體重變化 24
二、攝食量及飲水量 25
三、肝臟、腓腸肌及副睪脂肪的相對重量百分比 26
四、力竭表現 28
五、肌肉中過氧化產物malondialdehyde (MDA)及oxidized glutathione (GSSG) 29
六、血液生化數值 30
七、肌肉中發炎因子之基因表現量 31
八、肌肉中能量代謝及抗氧化因子之相關基因 32
九、RNA sequencing結果 34
1. 聚類熱圖分析(heatmap) 34
2. 差異表現基因(differential expression analyses) 36
3. Gene ontology (GO) analysis 39
第二節 短期下坡跑實驗結果 51
一、體重變化 51
二、攝食量及飲水量 52
三、肝臟、腓腸肌、脛前肌及副睪脂肪的相對重量百分比 53
四、力竭表現 55
五、肌肉中過氧化產物malondialdehyde (MDA) 56
六、血液生化數值 57
七、肌肉中發炎因子之基因表現量 58
1. 腓腸肌 58
2. 脛前肌 59
3. 比目魚肌 60
4. 伸趾長肌 61
八、肌肉中能量代謝及抗氧化因子之相關基因 62
1. 腓腸肌 62
2. 脛前肌 65
3. 比目魚肌 68
4. 伸趾長肌 70
第六章 討論 72
第一節 白藜蘆醇對力竭時間的影響 72
第二節 白藜蘆醇對肌肉中過氧化產物的影響 72
第三節 白藜蘆醇對肌肉損傷的影響 73
第四節 白藜蘆醇對肌肉中TNF-α及IL-6的影響 73
第五節 白藜蘆醇對肌肉中AMPK的影響 74
第六節 白藜蘆醇對肌肉中GLUT4的影響 75
第七節 白藜蘆醇對肌肉中SIRT1及PGC-1α的影響 76
第八節 RNA sequencing分析白藜蘆醇可能透過某些基因所帶來的影響 76
第七章 結論 78
第八章 參考文獻 79

 
圖目錄
Figure 1. Picture of the treadmill. 13
Figure 2. Experimental design of long-term downhill training 15
Figure 3. Experimental design of short-term downhill training 15
Figure 4. Training programs 16
Figure 5. Analysis process of RNA sequencing 21
Figure 6. Analysis projects of RNA sequencing 22
Figure 7. Body weight change during long-term experiment period 24
Figure 8. Food consumption and water intake during long-term experiment period 25
Figure 9. Effects of resveratrol on eccentric exercise-induced muscle damage on liver; gastrocnemius muscle and epididymal adipose tissue 27
Figure 10. Exhausted test in different groups 28
Figure 11. Malondialdehyde (MDA) and oxidized glutathione (GSSG) in different groups 29
Figure 12. Effects of resveratrol on eccentric exercise-induced muscle damage on Lactate dehydrogenase and Creatine kinase after non-loading swimming 30
Figure 13. Effects of resveratrol on long-term downhill running training on inflammatory mRNA expressions in gastrocnemius muscle 31
Figure 14. Effects of resveratrol on long-term downhill running training on energy utilization and anti-oxidative mRNA expression in gastrocnemius muscle 33
Figure 15. Heatmap representation of genes in different groups 34
Figure 16. Different genes expression between EX group and NC group 36
Figure 17. Different genes expression between EX+RES25 group and NC group 37
Figure 18. Different genes expression between EX+RES150 group and NC group 38
Figure 19. Gene ontology (GO) analysis of biological process in different groups vs NC group 40
Figure 20. Gene ontology (GO) analysis of molecular function in different groups vs NC group 42
Figure 21. Gene ontology (GO) analysis of cellular component in different groups vs NC group 44
Figure 22 Gene ontology (GO) analysis of biological process in EX+RES25 and EX+RES150 group vs EX group 45
Figure 23 Gene ontology (GO) analysis of molecular function in EX+RES25 and EX+RES150 group vs EX group 47
Figure 24 Gene ontology (GO) analysis of cellular component in EX+RES25 and EX+RES150 group vs EX group 49
Figure 25. Body weight change during short-term experiment period 51
Figure 26. Food consumption and water intake during short-term experiment period 52
Figure 27. Effects of resveratrol on eccentric exercise-induced muscle damage on liver; gastrocnemius muscle; tibialis anterior muscle and epididymal adipose tissue 54
Figure 28. Exhausted test in different groups 55
Figure 29. Malondialdehyde (MDA) in different muscles 56
Figure 30. Effects of resveratrol on eccentric exercise-induced muscle damage on Lactate dehydrogenase and Creatine kinase 57
Figure 31. Effects of resveratrol on short-term downhill running training on inflammatory mRNA expressions in gastrocnemius muscle 58
Figure 32. Effects of resveratrol on short-term downhill running training on inflammatory mRNA expressions in tibialis anterior muscle 59
Figure 33. Effects of resveratrol on short-term downhill running training on inflammatory mRNA expressions in soleus muscle 60
Figure 34. Effects of resveratrol on short-term downhill running training on inflammatory mRNA expressions in extensor digitorum longus muscle 61
Figure 35. Effects of resveratrol on short-term downhill running training on energy utilization and anti-oxidative mRNA expression in gastrocnemius muscle 63
Figure 36. Effects of resveratrol on short-term downhill running training on energy utilization and anti-oxidative mRNA expression in tibialis anterior muscle 66
Figure 37. Effects of resveratrol on short-term downhill running training on energy utilization and anti-oxidative mRNA expression in soleus muscle 69
Figure 38. Effects of resveratrol on short-term downhill running training on energy utilization and anti-oxidative mRNA expression in extensor digitorum longus muscle 71

 
表目錄
Table 1. Primers list for qPCR 19

1.         Nieman DC, Zwetsloot KA, Simonson AJ, Hoyle AT, Wang X, Nelson HK, Lefranc-Millot C, Guérin-Deremaux L: Effects of Whey and Pea Protein Supplementation on Post-Eccentric Exercise Muscle Damage: A Randomized Trial. Nutrients 2020, 12.
2.         Wang CC, Lin SC, Hsu SC, Yang MT, Chan KH: Effects of Creatine Supplementation on Muscle Strength and Optimal Individual Post-Activation Potentiation Time of the Upper Body in Canoeists. Nutrients 2017, 9.
3.         Malaguarnera L: Influence of Resveratrol on the Immune Response. Nutrients 2019, 11.
4.         Breuss JM, Atanasov AG, Uhrin P: Resveratrol and Its Effects on the Vascular System. Int J Mol Sci 2019, 20.
5.         O'Donoghue G, Blake C, Cunningham C, Lennon O, Perrotta C: What exercise prescription is optimal to improve body composition and cardiorespiratory fitness in adults living with obesity? A network meta-analysis. Obes Rev 2021, 22:e13137.
6.         Mujika I, Rønnestad BR, Martin DT: Effects of Increased Muscle Strength and Muscle Mass on Endurance-Cycling Performance. Int J Sports Physiol Perform 2016, 11:283-289.
7.         Reddigan JI, Ardern CI, Riddell MC, Kuk JL: Relation of physical activity to cardiovascular disease mortality and the influence of cardiometabolic risk factors. Am J Cardiol 2011, 108:1426-1431.
8.         Demakakos P, Hamer M, Stamatakis E, Steptoe A: Low-intensity physical activity is associated with reduced risk of incident type 2 diabetes in older adults: evidence from the English Longitudinal Study of Ageing. Diabetologia 2010, 53:1877-1885.
9.         Zhang Y, Li C, Zou L, Liu X, Song W: The Effects of Mind-Body Exercise on Cognitive Performance in Elderly: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health 2018, 15.
10.       Stricker PR, Faigenbaum AD, McCambridge TM: Resistance Training for Children and Adolescents. Pediatrics 2020, 145.
11.       Kirwan JP, Sacks J, Nieuwoudt S: The essential role of exercise in the management of type 2 diabetes. Cleve Clin J Med 2017, 84:S15-s21.
12.       Slentz CA, Aiken LB, Houmard JA, Bales CW, Johnson JL, Tanner CJ, Duscha BD, Kraus WE: Inactivity, exercise, and visceral fat. STRRIDE: a randomized, controlled study of exercise intensity and amount. J Appl Physiol (1985) 2005, 99:1613-1618.
13.       Admiraal WM, van Valkengoed IG, JS LdM, Stronks K, Hoekstra JB, Holleman F: The association of physical inactivity with Type 2 diabetes among different ethnic groups. Diabet Med 2011, 28:668-672.
14.       Beals JW, Kayser BD: When Exercising for Metabolic Health, the Work is Never Done, But HIIT Will Save You Time. J Clin Endocrinol Metab 2021, 106:e365-e366.
15.       Proske U, Morgan DL: Muscle damage from eccentric exercise: mechanism, mechanical signs, adaptation and clinical applications. J Physiol 2001, 537:333-345.
16.       Baumert P, Lake MJ, Stewart CE, Drust B, Erskine RM: Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing. Eur J Appl Physiol 2016, 116:1595-1625.
17.       Morgan DL, Allen DG: Early events in stretch-induced muscle damage. J Appl Physiol (1985) 1999, 87:2007-2015.
18.       Warren GL, Ingalls CP, Lowe DA, Armstrong RB: Excitation-contraction uncoupling: major role in contraction-induced muscle injury. Exerc Sport Sci Rev 2001, 29:82-87.
19.       Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM: M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 2000, 164:6166-6173.
20.       Peake JM, Neubauer O, Della Gatta PA, Nosaka K: Muscle damage and inflammation during recovery from exercise. J Appl Physiol (1985) 2017, 122:559-570.
21.       Dumont NA, Bentzinger CF, Sincennes MC, Rudnicki MA: Satellite Cells and Skeletal Muscle Regeneration. Compr Physiol 2015, 5:1027-1059.
22.       Metsios GS, Moe RH, Kitas GD: Exercise and inflammation. Best Pract Res Clin Rheumatol 2020, 34:101504.
23.       Muñoz-Cánoves P, Scheele C, Pedersen BK, Serrano AL: Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword? Febs j 2013, 280:4131-4148.
24.       Pedersen BK, Febbraio MA: Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev 2008, 88:1379-1406.
25.       Saltiel AR, Olefsky JM: Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest 2017, 127:1-4.
26.       Suzuki K: Chronic Inflammation as an Immunological Abnormality and Effectiveness of Exercise. Biomolecules 2019, 9.
27.       Andrade FH, Reid MB, Allen DG, Westerblad H: Effect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from the mouse. J Physiol 1998, 509 ( Pt 2):565-575.
28.       Sakellariou GK, Vasilaki A, Palomero J, Kayani A, Zibrik L, McArdle A, Jackson MJ: Studies of mitochondrial and nonmitochondrial sources implicate nicotinamide adenine dinucleotide phosphate oxidase(s) in the increased skeletal muscle superoxide generation that occurs during contractile activity. Antioxid Redox Signal 2013, 18:603-621.
29.       Kreher JB, Schwartz JB: Overtraining syndrome: a practical guide. Sports Health 2012, 4:128-138.
30.       Cheng AJ, Bruton JD, Lanner JT, Westerblad H: Antioxidant treatments do not improve force recovery after fatiguing stimulation of mouse skeletal muscle fibres. J Physiol 2015, 593:457-472.
31.       Tanskanen M, Atalay M, Uusitalo A: Altered oxidative stress in overtrained athletes. J Sports Sci 2010, 28:309-317.
32.       Yamada T, Abe M, Lee J, Tatebayashi D, Himori K, Kanzaki K, Wada M, Bruton JD, Westerblad H, Lanner JT: Muscle dysfunction associated with adjuvant-induced arthritis is prevented by antioxidant treatment. Skelet Muscle 2015, 5:20.
33.       Robergs RA, Pearson DR, Costill DL, Fink WJ, Pascoe DD, Benedict MA, Lambert CP, Zachweija JJ: Muscle glycogenolysis during differing intensities of weight-resistance exercise. J Appl Physiol (1985) 1991, 70:1700-1706.
34.       Puupponen-Pimiä R, Aura AM, Oksman-Caldentey KM, Myllärinen P, Saarela M, Mattila-Sandholm T, Poutanen K: Development of functional ingredients for gut health. Trends in Food Science & Technology 2002, 13:3-11.
35.       Neveu V, Perez-Jiménez J, Vos F, Crespy V, du Chaffaut L, Mennen L, Knox C, Eisner R, Cruz J, Wishart D, Scalbert A: Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford) 2010, 2010:bap024.
36.       Andrés-Lacueva C, Medina-Remon A, Llorach R, Urpi-Sarda M, Khan N, Chiva-Blanch G, Zamora-Ros R, Rotches-Ribalta M, Lamuela-Raventos RM: Phenolic compounds: chemistry and occurrence in fruits and vegetables. Fruit and vegetable phytochemicals: Chemistry, nutritional value and stability 2010, 1.
37.       Mackie R, White B: Gastrointestinal microbiology: Volume 1 gastrointestinal ecosystems and fermentations. Springer Science & Business Media; 2012.
38.       Manach C, Donovan JL: Pharmacokinetics and metabolism of dietary flavonoids in humans. Free Radic Res 2004, 38:771-785.
39.       Déprez S, Brezillon C, Rabot S, Philippe C, Mila I, Lapierre C, Scalbert A: Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids. J Nutr 2000, 130:2733-2738.
40.       Saura-Calixto F, Serrano J, Goñi I: Intake and bioaccessibility of total polyphenols in a whole diet. Food Chemistry 2007, 101:492-501.
41.       Hanhineva K, Törrönen R, Bondia-Pons I, Pekkinen J, Kolehmainen M, Mykkänen H, Poutanen K: Impact of dietary polyphenols on carbohydrate metabolism. Int J Mol Sci 2010, 11:1365-1402.
42.       Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N: Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Oxid Med Cell Longev 2016, 2016:7432797.
43.       Williams LD, Burdock GA, Edwards JA, Beck M, Bausch J: Safety studies conducted on high-purity trans-resveratrol in experimental animals. Food Chem Toxicol 2009, 47:2170-2182.
44.       Novelle MG, Wahl D, Diéguez C, Bernier M, de Cabo R: Resveratrol supplementation: Where are we now and where should we go? Ageing Res Rev 2015, 21:1-15.
45.       Springer M, Moco S: Resveratrol and Its Human Metabolites-Effects on Metabolic Health and Obesity. Nutrients 2019, 11.
46.       Hart N, Sarga L, Csende Z, Koltai E, Koch LG, Britton SL, Davies KJ, Kouretas D, Wessner B, Radak Z: Resveratrol enhances exercise training responses in rats selectively bred for high running performance. Food Chem Toxicol 2013, 61:53-59.
47.       McAnulty LS, Miller LE, Hosick PA, Utter AC, Quindry JC, McAnulty SR: Effect of resveratrol and quercetin supplementation on redox status and inflammation after exercise. Appl Physiol Nutr Metab 2013, 38:760-765.
48.       Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, Agarwal B, Ye L, Ramadori G, Teodoro JS, et al: SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 2012, 15:675-690.
49.       Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, et al: Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006, 127:1109-1122.
50.       Ungvari Z, Labinskyy N, Mukhopadhyay P, Pinto JT, Bagi Z, Ballabh P, Zhang C, Pacher P, Csiszar A: Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol Heart Circ Physiol 2009, 297:H1876-1881.
51.       Rabinovitch RC, Samborska B, Faubert B, Ma EH, Gravel SP, Andrzejewski S, Raissi TC, Pause A, St-Pierre J, Jones RG: AMPK Maintains Cellular Metabolic Homeostasis through Regulation of Mitochondrial Reactive Oxygen Species. Cell Rep 2017, 21:1-9.
52.       Galiniak S, Aebisher D, Bartusik-Aebisher D: Health benefits of resveratrol administration. Acta Biochim Pol 2019, 66:13-21.
53.       Thomson DM: The Role of AMPK in the Regulation of Skeletal Muscle Size, Hypertrophy, and Regeneration. Int J Mol Sci 2018, 19.
54.       Huang CC, Liu CC, Tsao JP, Hsu CL, Cheng IS: Effects of Oral Resveratrol Supplementation on Glycogen Replenishment and Mitochondria Biogenesis in Exercised Human Skeletal Muscle. Nutrients 2020, 12.
55.       Kan NW, Ho CS, Chiu YS, Huang WC, Chen PY, Tung YT, Huang CC: Effects of Resveratrol Supplementation and Exercise Training on Exercise Performance in Middle-Aged Mice. Molecules 2016, 21.
56.       Pappireddi N, Martin L, Wühr M: A Review on Quantitative Multiplexed Proteomics. Chembiochem 2019, 20:1210-1224.
57.       Shah R, Yeri A, Das A, Courtright-Lim A, Ziegler O, Gervino E, Ocel J, Quintero-Pinzon P, Wooster L, Bailey CS, et al: Small RNA-seq during acute maximal exercise reveal RNAs involved in vascular inflammation and cardiometabolic health: brief report. Am J Physiol Heart Circ Physiol 2017, 313:H1162-h1167.
58.       Urdinguio RG, Tejedor JR, Fernández-Sanjurjo M, Pérez RF, Peñarroya A, Ferrero C, Codina-Martínez H, Díez-Planelles C, Pinto-Hernández P, Castilla-Silgado J, et al: Physical exercise shapes the mouse brain epigenome. Mol Metab 2021, 54:101398.
59.       Zhang SS, Zhu L, Peng Y, Zhang L, Chao FL, Jiang L, Xiao Q, Liang X, Tang J, Yang H, et al: Long-term running exercise improves cognitive function and promotes microglial glucose metabolism and morphological plasticity in the hippocampus of APP/PS1 mice. J Neuroinflammation 2022, 19:34.
60.       Kuipers H, Verstappen FT, Keizer HA, Geurten P, van Kranenburg G: Variability of aerobic performance in the laboratory and its physiologic correlates. Int J Sports Med 1985, 6:197-201.
61.       Ferreira JC, Rolim NP, Bartholomeu JB, Gobatto CA, Kokubun E, Brum PC: Maximal lactate steady state in running mice: effect of exercise training. Clin Exp Pharmacol Physiol 2007, 34:760-765.
62.       Aguilar Diaz De Leon J, Borges CR: Evaluation of Oxidative Stress in Biological Samples Using the Thiobarbituric Acid Reactive Substances Assay. J Vis Exp 2020.
63.       Wu RE, Huang WC, Liao CC, Chang YK, Kan NW, Huang CC: Resveratrol protects against physical fatigue and improves exercise performance in mice. Molecules 2013, 18:4689-4702.
64.       Jahangiri Z, Gholamnezhad Z, Hosseini M, Beheshti F, Kasraie N: The effects of moderate exercise and overtraining on learning and memory, hippocampal inflammatory cytokine levels, and brain oxidative stress markers in rats. J Physiol Sci 2019, 69:993-1004.
65.       Guo Y, Wang A, Liu X, Li E: Effects of resveratrol on reducing spermatogenic dysfunction caused by high-intensity exercise. Reprod Biol Endocrinol 2019, 17:42.
66.       Xiao NN: Effects of Resveratrol Supplementation on Oxidative Damage and Lipid Peroxidation Induced by Strenuous Exercise in Rats. Biomol Ther (Seoul) 2015, 23:374-378.
67.       Del Rio D, Stewart AJ, Pellegrini N: A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005, 15:316-328.
68.       Tsao JP, Liu CC, Wang HF, Bernard JR, Huang CC, Cheng IS: Oral Resveratrol supplementation attenuates exercise-induced Interleukin-6 but not Oxidative Stress after a high intensity cycling challenge in adults. Int J Med Sci 2021, 18:2137-2145.
69.       Wilson IJ, Burchell RK, Worth AJ, Burton SE, Gedye KR, Clark KJ, Crosse KR, Jack M, Odom TF, De Grey SJ, et al: Kinetics of Plasma Cell-Free DNA and Creatine Kinase in a Canine Model of Tissue Injury. J Vet Intern Med 2018, 32:157-164.
70.       Tomazoni SS, Machado C, De Marchi T, Casalechi HL, Bjordal JM, de Carvalho PTC, Leal-Junior ECP: Infrared Low-Level Laser Therapy (Photobiomodulation Therapy) before Intense Progressive Running Test of High-Level Soccer Players: Effects on Functional, Muscle Damage, Inflammatory, and Oxidative Stress Markers-A Randomized Controlled Trial. Oxid Med Cell Longev 2019, 2019:6239058.
71.       Helge JW, Stallknecht B, Pedersen BK, Galbo H, Kiens B, Richter EA: The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle. J Physiol 2003, 546:299-305.
72.       Marko DM, Foran G, Vlavcheski F, Baron DC, Hayward GC, Baranowski BJ, Necakov A, Tsiani E, MacPherson REK: Interleukin-6 Treatment Results in GLUT4 Translocation and AMPK Phosphorylation in Neuronal SH-SY5Y Cells. Cells 2020, 9.
73.       Ikeda SI, Tamura Y, Kakehi S, Sanada H, Kawamori R, Watada H: Exercise-induced increase in IL-6 level enhances GLUT4 expression and insulin sensitivity in mouse skeletal muscle. Biochem Biophys Res Commun 2016, 473:947-952.
74.       Hawley JA, Lundby C, Cotter JD, Burke LM: Maximizing Cellular Adaptation to Endurance Exercise in Skeletal Muscle. Cell Metab 2018, 27:962-976.
75.       Kristensen DE, Albers PH, Prats C, Baba O, Birk JB, Wojtaszewski JF: Human muscle fibre type-specific regulation of AMPK and downstream targets by exercise. J Physiol 2015, 593:2053-2069.
76.       Tarini VA, Carnevali LC, Jr., Arida RM, Cunha CA, Alves ES, Seeleander MC, Schmidt B, Faloppa F: Effect of exhaustive ultra-endurance exercise in muscular glycogen and both Alpha1 and Alpha2 Ampk protein expression in trained rats. J Physiol Biochem 2013, 69:429-440.
77.       Guo J, Pereira TJ, Mori Y, Gonzalez Medina M, Breen DM, Dalvi PS, Zhang H, McCole DF, McBurney MW, Heximer SP, et al: Resveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK. J Vasc Res 2020, 57:325-340.
78.       Vlavcheski F, Den Hartogh DJ, Giacca A, Tsiani E: Amelioration of High-Insulin-Induced Skeletal Muscle Cell Insulin Resistance by Resveratrol Is Linked to Activation of AMPK and Restoration of GLUT4 Translocation. Nutrients 2020, 12.
79.       Stuart CA, Howell ME, Baker JD, Dykes RJ, Duffourc MM, Ramsey MW, Stone MH: Cycle training increased GLUT4 and activation of mammalian target of rapamycin in fast twitch muscle fibers. Med Sci Sports Exerc 2010, 42:96-106.
80.       Pereira BC, da Rocha AL, Pinto AP, Pauli JR, de Moura LP, Mekary RA, de Freitas EC, da Silva AS: Excessive training impairs the insulin signal transduction in mice skeletal muscles. J Endocrinol 2016, 230:93-104.
81.       Sakamoto J, Miura T, Shimamoto K, Horio Y: Predominant expression of Sir2α, an NAD-dependent histone deacetylase, in the embryonic mouse heart and brain. FEBS letters 2004, 556:281-286.
82.       Waldman M, Cohen K, Yadin D, Nudelman V, Gorfil D, Laniado-Schwartzman M, Kornwoski R, Aravot D, Abraham NG, Arad M: Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving ‘SIRT1 and PGC-1α’. Cardiovascular diabetology 2018, 17:1-12.
83.       Sin TK, Yu AP, Yung BY, Yip SP, Chan LW, Wong CS, Rudd JA, Siu PM: Effects of long-term resveratrol-induced SIRT1 activation on insulin and apoptotic signalling in aged skeletal muscle. Acta Diabetol 2015, 52:1063-1075.
84.       Higashida K, Kim SH, Jung SR, Asaka M, Holloszy JO, Han DH: Effects of resveratrol and SIRT1 on PGC-1α activity and mitochondrial biogenesis: a reevaluation. PLoS Biol 2013, 11:e1001603.
85.       Nishigaki A, Kido T, Kida N, Kakita-Kobayashi M, Tsubokura H, Hisamatsu Y, Okada H: Resveratrol protects mitochondrial quantity by activating SIRT1/PGC-1α expression during ovarian hypoxia. Reprod Med Biol 2020, 19:189-197.
86.       Lu L, Sun K, Chen X, Zhao Y, Wang L, Zhou L, Sun H, Wang H: Genome-wide survey by ChIP-seq reveals YY1 regulation of lincRNAs in skeletal myogenesis. Embo j 2013, 32:2575-2588.
87.       Feng S, Wan S, Liu S, Wang W, Tang M, Bai L, Zhu Y: LARS2 Regulates Apoptosis via ROS-Mediated Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Ovarian Granulosa Cells. Oxid Med Cell Longev 2022, 2022:5501346.