1.1)渭南师范学院体育学院,渭南 714099;2.2)陕西师范大学体育学院暨运动生物学研究所,西安 710119
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陕西省科技厅科研计划项目(2021JQ-827)、陕西省教育厅科研计划项目(20JK0633)资助.
1.1)School of Physical Education, Weinan Normal University, Weinan 714099, China;2.2)Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an 710119, China
This study was funded by Scientific Research Project of Science and Technology Department of Shaanxi Province, China (2021JQ-827) and Scientific Research Special Project of Shaanxi Provincial Department of Education, China (20JK0633).
为探讨有氧运动对心梗大鼠心功能的影响,将3月龄SD雄性大鼠适应性喂养1周后随机分为正常组(C组)、假手术组(S组)、心梗安静组(MI组)、正常+运动组(CE组)、心梗+运动组(ME组),每组8只. MI组结扎左冠状动脉前降支制备心梗模型;S组只穿线不结扎;CE组与ME组术后1周开始有氧训练,运动方式为依次以10 m/min×10 min,13 m/min× 10 min,16 m/min×40 min进行跑台训练,60 min/d,每周5 d,连续4周. 训练结束后次日,采用血流动力学检测左室收缩压(left ventricular systolic pressure,LVSP)、左室舒张末压(left ventricular end-diastolic pressure,LVEDP)和收缩/舒张速率(±dp/dtmax)等心功能相关指标,单细胞可视化动缘探测系统(IonOptix)测定[Ca2+]i变化百分数([Ca2+]i amplitude)、[Ca2+]i荧光比率(ratio)、达峰速率(departure velocity)、达峰时程(time to peak,TTP)、达峰50%时程(time to peak 50%,TTP50%)、达基线50%时程(time to baseline50%,TTB50%)、达基线速率(return velocity)以及ratio改变幅度(ratio amplitude)等钙瞬变指标和肌节最大收缩及舒张速率(±dl/dtmax)、肌节长度(sarcomere length,SL)、肌节收缩幅度(peak twitch amplitude,PTA)、肌节缩短分数(SL shortening%)等心肌细胞收缩指标,蛋白质印迹(Western blotting)方法检测PI3K-Akt-PKG-1/p-PLN-SERCA2a信号通路及细胞凋亡相关蛋白. 与S组相比,MI组PI3K-Akt-PKG-1/p-PLN-SERCA2a信号通路被显著抑制,心肌细胞凋亡显著增加,LVEDP显著升高,LVSP和±dp/dtmax显著降低,[Ca2+]i amplitude、ratio amplitude、departure velocity和return velocity均显著下降,TTB50%、TTP和TTP50%均显著增加,心肌细胞SL shortening%、PTA、±dl/dtmax均显著减少;与MI组相比,ME组PI3K-Akt-PKG-1/p-PLN-SERCA2a信号通路显著被激活,细胞凋亡显著被抑制,LVEDP显著降低,LVSP和±dp/dtmax显著升高,ratio amplitude、[Ca2+]i amplitude、ratio velocity和departure velocity均显著提高,TB50%、TTP和TTP50%均显著缩短,心肌细胞SL Shortening%、PTA、±dl/dtmax均显著提高. 上述结果表明,有氧运动改善MI大鼠梗死周边区心肌细胞的钙瞬变和收缩功能异常,并激活PI3K-Akt-PKG-1/p-PLN-SERCA2a信号,抑制心肌细胞凋亡,改善心梗心功能,且心梗心功能的改善与PI3K-Akt-PKG-1/p-PLN-SERCA2a信号通路激活和心肌细胞凋亡抑制关系密切.
To investigate the effect of aerobic exercise on cardiac function in myocardial infarction rats, SD male rats were randomly divided into normal group (C group), sham operation group (S group), myocardial infarction group (MI group), normal+exercise group (CE group) and myocardial infarction+exercise group (ME group) after 1 week of adaptive feeding. Then, an MI model was established by ligating the left anterior descending coronary artery and group S only threading without ligation. One week after surgery, animals were randomly assigned to receive 4 weeks of no training or training (1 h/d, 5 d/week on a treadmill). In detail, the training consisted of two 10-minute sessions at speed of 10 m/min and 13 m/min, and the remaining 40 min at speed of 16 m/min. The next day after the training, blood flow mechanics was used to detect cardiac function. A single cell visual moving edge detection system (Ion Optix) was used to determine [Ca2+]i amplitude, [Ca2+]i fluorescence ratio, departure velocity, time to peak(TTP), time to peak50%(TTP50%), time to baseline50%(TTB50%), return velocity, ratio amplitude, maximum contraction and diastolic rate of sarcomere(±dl/dtmax), sarcomere length(SL), peak twitch amplitude(PTA) and SL shortening%. The related proteins of PI3K-AKT-PKG-1/p-PLN-SERCA2a signaling pathway and apoptosis were detected by PI3K-AKT-PKG-1/p-PLN-SERCA2a signaling pathway and apoptosis related proteins were detected by Western blotting. Compared with group S, in group MI, PI3K-Akt-PKG-1/p-PLN-SERCA2a signaling pathway is significantly inhibited, apoptosis and left ventricular end-diastolic pressure (LVEDP) are significantly increased, left ventricular systolic pressure (LVSP) and maximum pressure increasing and decreasing rate(±dp/dtmax), [Ca2+]i amplitude, [Ca2+]i ratio amplitude, departure velocity and return velocity all significantly reduce, and TTB50%, TTP and TTP50% both significantly increase. The myocardial cells were significantly reduced at the SL shortening%, PTA, ±dp/dtmax. Compared with MI group, PI3K-Akt-PKG-1/p-PLN-SERCA2a signaling pathway in ME group is significantly activated, apoptosis and LVEDP are significantly reduced, LVSP and ±dp/dtmax are significantly increased, ratio amplitude, [Ca2+]i amplitude, ratio velocity and departure velocity are significantly increased, and TB50%, TTP and TTP50% are significantly shortened. The myocardial cells were significantly inaeased at the SL shortening%, PTA, ±dp/dtmax. It can be concluded that aerobic exercise improves the calcium transient and myocardial systolic function in peripheral infarction area of MI rats, activates the PI3K-Akt-PKG-1/p-PLN-SERCA2a signal, inhibits the apoptosis of myocardial cells, and improves myocardial infarction function. Moreover, the improvement of myocardial infarction function is closely related to the activation of PI3K-Akt-PKG-1/p-PLN-SERCA2a signaling pathway and the inhibition of myocardial cell apoptosis.
刘纽,田振军.心梗大鼠通过有氧运动激活PI3K-Akt-PKG-1/p-PLN-SERCA2a通路抑制心肌细胞凋亡改善心功能[J].生物化学与生物物理进展,2021,48(6):698-708
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