摘要
世界三大疾病之一的心血管疾病正严重影响着人类、尤其是中老年人的健康,如何延缓衰老、提高老年人健康寿命的问题正逐渐成为医学、生物学乃至运动科学领域研究的热点。相对药物防治的高昂成本,体育锻炼无疑是廉价而又令人愉快的防治手段。适宜强度的训练能使心肌产生适应性肥大,且这种肥大与病理性心肌肥大在形态和功能上有着本质的差异,这为通过训练改善因衰老而引起的心肌细胞数量减少和功能下降提供了理论基础。
传统的观点认为细胞凋亡不发生于诸如成熟的心肌细胞、神经细胞等不具备再生能力的细胞中。但自20世纪80年代末开始的研究显示,细胞凋亡同样存在于心肌细胞中。心肌细胞凋亡在心脏的发育、缺血-再灌注损伤、自发性高血压、心律失常、心力衰竭、心肌Sarcopenia等许多与心脏有关的生理病理中起到十分重要的作用,被认为是心脏由代偿性变化向病理性变化发展的细胞生物学基础。
TNF-α是一种多效促炎性细胞因子,在炎症、免疫调节反应、细胞增殖与分化以及抗病毒反应中发挥作用。近年来,对TNF-α的研究多关注其在炎症、免疫方面的效应,而运动对其介导的细胞凋亡的影响较少涉及心肌组织。
目的：探讨28周的耐力、抗阻和混合训练对TNF-α介导的C57BL/6小鼠心肌细胞凋亡通路上的信号分子Caspase-8、Caspase-3及NF-κBmRNA表达的影响；观察3种形式的训练对C57BL/6小鼠心肌细胞形态的影响。
方法：将32只雄性C57BL/6小鼠随机分为耐力训练组(E,n=8)、抗阻训练组(R,n=8)、混合训练组(M,n=8)以及安静对照组(C,n=8)。实验持续28周,所有训练组均是周一、三、五、日训练。其中,耐力训练组进行无负重跑台训练,速度由0.8 km/h逐渐增至1.0 km/h,每次训练时间为30min；抗阻训练组采用负重爬梯训练模式,尾部负重量由自身体重的10%逐渐增至150%,最后4周再降至自身体重的120%；混合训练组周一、五进行抗阻训练,周三、日进行耐力训练形式,运动量和运动强度与当周抗阻、耐力组一致。
结果：
(1)28周后,小鼠体重都随时间显著性增加,训练组心系数均高于安静对照组；
(2)3种形式的训练均下调了小鼠心肌TNF-αmRNA的表达水平,耐力训练组与安静对照组相比具有极显著性差异(P<0.01),而抗阻和混合训练组与安静对照组之间也有显著性差异(P<0.05)；
(3)3种形式的训练均下调了小鼠心肌Caspase-8mRNA的表达水平,耐力和抗阻训练组与安静对照组之间具有极显著性差异(P<0.01),而混合组无明显差异(P>0.05)；
(4)3种形式的训练均下调了小鼠心肌Caspase-3mRNA的表达水平,耐力训练组与安静对照组之间具有显著性差异(P<0.05),抗阻和混合训练组则无显著性变化(P>0.05)；
(5)耐力和混合训练显著上调了小鼠心肌NF-KBmRNA的表达(P<0.05),但抗阻训练组无显著性变化(P>0.05)。
结论：
(1)训练影响了C57BL/6小鼠体重的变化。安静对照组体重较训练组显著增加,可能是由于体脂增多所致,而耐力训练组体重变化最小意味着耐力训练对体重控制的机制可能与其对脂类代谢的有效调控有关。
(2)3种形式的训练均使得小鼠心肌的比重(即心系数)增加,可认为适宜强度的训练能够使心肌产生适应性肥大。
(3)3种训练模式中,耐力训练使得促进心肌细胞凋亡的信号分子TNF-α、Caspase-8、Caspase-3mRNA在小鼠心肌的表达水平显著下调,而抗凋亡的信号分子NF-KBmRNA在小鼠心肌的表达水平显著上调,提示耐力训练模式是有效刺激心肌适应性肥大、抑制心肌细胞凋亡、延缓心肌衰老的运动方式。
(4)抗阻和混合训练对TNF-α介导的心肌细胞凋亡通路上相关信号分子的影响不都具有显著性,提示在抑制心肌细胞凋亡、延缓心肌衰老的过程中,两者的作用不如耐力训练明显。
As one of the world's three major diseases, cardiovascular disease is seriously affecting human health, especially the elderly people. Delaying aging and improving life of the elderly people are becoming hot spots in medical, biological and even the field of sports science in the future. By contrast with drug prevention and treatment, physical activity is undoubtedly cheaper and more enjoyable. Appropriate exercise improves cardiac hypertrophy, which is different from pathological cardiac hypertrophy in morphology and function. This provides a theoretical basis on improving the number and function of the cardiac myocyte through exercise.
In traditional thoughts, apoptosis doesn't exist in the mature cells which doesn't have regenerative capacity, such as cardiac myocyte and nerve cells. However, in late 1980's, studies had shown that apoptosis also exists in cardiac myocyte. Cardiac apoptosis plays an important role in the pathophysiology of heart development, ischemia-reperfusion injury, spontaneous hypertension, arrhythmia, heart failure, cardiac muscle sarcopenia and many other heart-related diseases. And cardiac apoptosis have been considered as the cellular basis in the change from compensatory to pathological.
TNF-αis a pleiotropic pro-inflammatory cytokines and plays an important role in inflammation, immune response regulation, cell proliferation/differentiation and anti-viral response. Recent years, the studies of TNF-αpaid more attention in inflammation and immunological aspects, while there were very few studies about the effects of exercise on the apoptosis pathway which mediated by TNF-αin cardiac myocyte.
Objective:One aim of this study is to investigate the effects of 28-week endurance, resistance and mixed training on the expression of the signal molecules Caspase-8、Caspase-3 and NF-κBmRNA in the apoptosis pathway which mediated by TNF-a in the cardiac myocyte of C57BL/6 mice. The other is to observe the effects of 3 different of forms of trainging on cardiac myocyte in morphology.
Methods:32 male C57BL/6 mice were randomly assigned to endurance training group(E, n=8), resistance training group(R, n=8), mixed-training group(M, n=8) and control group (C, n=8). All the training groups were trained on Monday, Wednesday, Friday and Sunday per week and last for 28 weeks. Endurance training group mice were accustomed to treadmill training with no weight bearing, and with a speed from 0.8km/h to 1.2km/h gradually for 30min; resistance training group mice were engaged climbing training by weighted at the end of tails from 10% of its own weight to 150% gradually and then to 120% in the last 4 weeks; mixed-training group mice were to engaged climbing training on Monday, Friday, and engaged endurance training on Wednesday and Sunday.
Results:
(1)The body weight of mice were significantly increased after 28 weeks and the heart index of training groups were higher than the control group.
(2)3 different forms of training reduced TNF-αmRNA expression in cardiac myocyte of C57BL/6 mice. Endurance training group had very significant difference with the control group(P<0.01), while resistance training group and mix training group also had significant difference(P<0.05).
(3)3 different forms of training reduced Caspase-8mRNA expression in cardiac myocyte of C57BL/6 mice. Endurance and resistance training group both had very significant differences with the control group(P<0.01), while mix training group didn't(P>0.05).
(4)3 different forms of training reduced Caspase-3mRNA expression in cardiac myocyte of C57BL/6 mice. Endurance training group had a significant difference with the control group(P<0.05), while resistance and mix training group didn't(P>0.05).
(5)Endurance and mix training increased NF-KBmRNA expression in cardiac myocyte of C57BL/6 mice with significant difference(P<0.05), while the resistance training group had no significant change(P>0.05).
Conclusion:
(1)3 different forms of training have effect on the body weight of C57BL/6 mice.The reason why the body weight of control group mice increased significantly may probably due to an increase in the body fat. The body weight of endurance training group mice were the lowest among groups, meant that the mechanism of weight control by endurance training may have relation with the effective regulation of lipid metabolism.
(2)3 different forms of trainings increased the heart index of C57BL/6 mice. It can be considered that appropriate training improves cardiac hypertrophy.
(3)Endurance training reduced TNF-α, Caspase-8, Caspase-3mRNA expression in cardiac myocyte of C57BL/6 mice significantly, while increased NF-KBmRNA expression significantly among 3 traing groups. It is indicated that endurance training is effective in stimulating cardiac hypertrophy, inhibiting cardiac apoptosis and delaying myocardial aging.
(4)The effects of resistance and mix training on the signal molecules in the apoptosis pathway which mediated by TNF-αin the cardiac myocyte were not all significant. It is indicated that the 2 forms of training didn't have the same effect on inhibiting cardiac apoptosis and delaying myocardial aging.
引文
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