收稿日期: 2016-04-19
网络出版日期: 2016-06-30
Effects of exercise on cardiac function and differential expression of circulating miRNAs in rats with acute myocardial infarction
Received date: 2016-04-19
Online published: 2016-06-30
研究不同运动强度对急性心肌梗死大鼠心功能的影响, 分析循环微小RNA(microRNAs, miRNAs)的差异表达与靶基因及基因功能. 制作急性心肌梗死大鼠模型40只,分为4组, 每组10只, 分别为假手术组、单纯心肌梗死组、中等强度持续运动(continuous moderate training, CMT)组和间歇高强度运动(high intensity interval training, HIT)组, CMT组和HIT组大鼠接受运动治疗8周, 用超声心动图评估心功能, 用基因芯片技术测定4组大鼠模型循环miRNAs差异表达, 用生物信息学技术分析不同运动强度下循环miRNAs相关靶基因及基因功能. CMT组和HIT组的治疗显著改善了心肌梗死大鼠心功能和运动耐量, HIT组显著优于CMT组. 单纯心肌梗死组与假手术组相比, 明显上调的循环miRNAs有14个, 明显下调的循环miRNAs有4个. 与单纯心肌梗死组相比, CMT组明显上调的循环miRNAs有11个, 明显下调的循环miRNAs有2个; HIT组明显上调的循环miRNAs有53个, 明显下调的关键miRNAs有41个. 与假手术组相比, 单纯心肌梗死组心肌相关循环miRNAs的差异表达有miR-26a-5p, miR-92a-3p和miR-378a-3p; 与单纯心肌梗死组相比, CMT组有miR-92a-3p, HIT组有miR-34c-3p, miR-23a-3p, miR-98-3p, miR-208a-5p和miR-92-3p. 高强度间歇运动对心肌梗死大鼠心功能和运动耐量的改善作用优于中等强度持续运动, 其循环miRNAs及心肌相关循环miRNAs的差异表达数量明显高于中等强度持续运动, 循环miRNAs差异表达有望作为运动强度和运动效果判断的分子生物学标志物.
夏昆1, 丁荣晶2, 陆凯3, 王历4 . 不同运动强度对急性心肌梗死大鼠心功能的影响及循环miRNAs差异表达[J]. 上海大学学报(自然科学版), 2016 , 22(3) : 344 -356 . DOI: 10.3969/j.issn.1007-2861.2016.03.010
To study the effects of different exercise intensity on cardiac function and differential expression of circulating microRNAs (miRNAs), target genes and gene function in rats with acute myocardial infarction (AMI). Establish AMI models with 40 rats, divide them into 4 groups, such as Sham operation group, isolated myocardial infarction group, continuous moderately training (CMT) group, and high intensity interval training (HIT) group, with 10 AMI rats in each group. CMT and HIT groups received exercise therapies for 8 weeks. Evaluate cardiac function with echocardiography. Analyze differential expression of circulating microRNAs, related target genes and gene function using miRNAs microarray and bioinformatics technology. CMT and HIT therapies significantly improved cardiac function and exercise tolerance in AMI rats. The effect of HIT group is significantly better than that of CMT group. Compared with Sham operation group, 14 circulating miRNAs were obviously up-regulated, 4 circulating miRNAs were obviously down-regulated in isolated myocardial infarction group. Compared with isolated myocardial infarction group, 11 circulating miRNAs were obviously up-regulated, 2 circulating miRNAs were obviously down-regulated in CMT group, and 53 circulating miRNAs were obviously up-regulated, 41 key miRNAs were obviously down-regulated in HIT group. Compared with Sham operation group, differential expression of myocardium related circulating miRNAs in isolated myocardial infarction group are miR-26a-5p, miR-92a-3p and miR-378a-3p. Compared with isolated myocardial infarction group, there is miR-92a-3p in CMT group, and there are miR-34c-3p, miR-23a-3p, miR-98-3p, miR-208a-5p and miR-92-3p in HIT group. HIT improving cardiac function and exercise tolerance in AMI rats are better than those of CMT. Numbers of differential expression of circulating miRNAs and myocardium related circulating miRNAs with HIT are higher than those of CMT, indicating that circulating miRNAs are expected to be biomarkers for determining exercise intensity and exercise effect.
[1] Oldridge N. Exercise-based cardiac rehabilitation in patients with coronary heart disease: Meta-analysis outcomes revisited [J]. Future Cardiol, 2012, 8: 729-751.
[2] Moholdt T, Aamot I L, Granøien I, et al. Aerobic interval training increases peak oxygen uptake more than usual care exercise training in myocardial infarction patients: a randomized
controlled study [J]. Clin Rehabil, 2012, 26: 33-44.
[3] Moholdt T, Aamot I L, Granøien I, et al. Long-term follow-up after cardiac rehabilitation: a randomized study of usual care exercise training versus aerobic interval training after myocardial infarction [J]. Int J Cardiol, 2011, 152: 388-390.
[4] Maiorana A. Interval training confers greater gains than continuous training in people with heart failure [J]. J Physiother, 2012, 58: 199.
[5] Wang G K, Zhu J Q, Zhang J T, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans [J]. Eur Heart J, 2010, 31(6): 659-666.
[6] Corsten M F, Dennert R, Jochems S, et al. Circulating microRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease [J]. Circ Cardiovasc Genet, 2010, 3(6): 499-506.
[7] Adachi T, Nakanishi M, Otsuka Y, et al. Plasma microRNA-499 as a biomarker of acute myocardial infarction [J]. Clin Chem, 2010, 56(7): 1183-1185.
[8] Ma Z, Qi J, Meng S, et al. Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway [J]. Eur J Appl Pysiciol, 2013, 113: 2473-2486.
[9] Martinelli N C, Cohen C R, Santos K G, et al. An analysis of the gobal expression of microRNAs in an experimental model of physiological left ventricular hypertrophy [J]. PLoS
One, 2014, 9: e93271.
[10] Høydal M A, Wisløff U, Kemi O J, et al. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training [J]. Eur J Cardiovasc Prev Rehabil, 2007, 14: 753-760.
[11] Kraljevic J, Marinovic J, Pravdic D, et al. Aerobic interval training attenuates remodelling and mitochondrial dysfunction in the post-infarction failing rat heart [J]. Cardiovasc Res, 2013, 99: 55-64.
[12] Moreira J B, Bechara L R, Bozi L H, et al. High-versus moderate-intensity aerobic exercise training effects on skeletal muscle of infarcted rats [J]. J Appl Physiol, 2013, 114: 1029-1041.
[13] Fernandes T, Bara?na V G, Negrão E, et al. Aerobic exercise training promotes physiological remodeling a set of microRNAs [J]. Am J Physiol Heart Circ Physiol, 2015, 309: 543-552.
[14] Seeger F H, Zeiher A M, Dimmeler S. MicroRNA in stem cell function and regenerative therapy of the heart [J]. Arterioscler Thromb Vasc Biol, 2013, 33: 1739-1746.
[15] Boon R A, Dimmeler S. MicroRNA in myocardial infarction [J]. Natrure Review Cardiology, 2015, 12: 135-142.
[16] Laterza O F, Lim L, Garrett-Engele P W, et al. Plasma microRNAs as sensitive and specific biomarkers of tissue injury [J]. Clin Chem, 2009, 55(11): 1977-1983.
[17] Mitchell P S, Parkin R K, Kroh E M, et al. Circulating microRNAs as stable blood-based markers for cancer detection [J]. Proc Natl Acad Sci USA, 2008, 105(30): 10513-10518.
[18] Hunter M P, Ismail N, Zhang X, et al. Detection of microRNAs expression in human peripheral blood microvesicles [J]. PLoS One, 2008, 3(11): e3694.
[19] Timmons J A, Jansson E, Fischer H, et al. Modulation of extracellular matrix genes reflects the magnitude of physiological adaptation to aerobic exercise training in humans [J]. BMC Biol, 2005, 3: 19.
[20] Keller P, Vollaard N, Babraj J, et al. Using systems biology to define the essential biological networks responsible for adaptation to endurance exercise training [J]. Biochem Soc Trans, 2007, 35(Pt5): 1306-1309.
[21] Leon A S, Franklin B A, Costa F, et al. Cardiac rehabilitation and secondary prevention of coronary heart disease: an American Heart Association scientific statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), in collaboration with the American Association of Cardiovascular and Pulmonary Rehabilitation [J]. Circulation, 2005, 111(3): 369-376.
[22] Corrà U, Piepoli M F, Carr´e F, et al. Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation [J]. Eur Heart J, 2010, 31(16): 1967-1974.
[23] 中华医学会心血管病学分会, 中国康复医学会心血管病专业委员会, 中国老年学学会心脑血管病专业委员会. 冠心病心脏康复与二级预防中国专家共识[J]. 中华心血管病杂志, 2013, 41(4): 267-275.
[24] Golbidi S, Laher I. Exercise and the cardiovascular system [J]. Cardiol Res Pract, 2012, 2012:201-206.
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