Geng Xiao, Zhao Honglin, Zhang Shumiao, Li Juan, Tian Fei, Feng Na, Fan Rong, Jia Min, Guo Haitao, Cheng Liang, Liu Jincheng, Chen Wensheng, Pei Jianming
Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
Department of Physical Education, Chang'an University, Xi'an, Shaanxi Province, China.
PLoS One. 2017 Mar 16;12(3):e0170463. doi: 10.1371/journal.pone.0170463. eCollection 2017.
The present study was designed to test the hypothesis that exercise training elicited a cardioprotective effect against ischemia and reperfusion (I/R) via the κ-opioid receptor (κ-OR)-mediated signaling pathway. Rats were randomly divided into four groups: the control group, the moderate intensity exercise (ME) group, the high intensity exercise (HE) group, and the acute exercise (AE) group. For the exercise training protocols, the rats were subjected to one week of adaptive treadmill training, while from the second week, the ME and HE groups were subjected to eight weeks of exercise training, and the AE group was subjected to three days of adaptive treadmill training and one day of vigorous exercise. After these protocols, the three exercise training groups were divided into different treatment groups, and the rats were subjected to 30 min of ischemia and 120 min of reperfusion. Changes in infarct size and serum cTnT (cardiac troponin T) caused by I/R were reduced by exercise training. Moreover, cardiac dysfunction caused by I/R was also alleviated by exercise training. These effects of exercise training were reversed by nor-BNI (a selective κ-OR antagonist), Compound C (a selective AMPK inhibitor), Akt inhibitor and L-NAME (a non-selective eNOS inhibitor). Expression of κ-OR and phosphorylation of AMPK, Akt and eNOS were significantly increased in the ME, HE and AE groups. These findings demonstrated that the cardioprotective effect of exercise training is possibly mediated by the κ-OR-AMPK-Akt-eNOS signaling pathway.
运动训练通过κ-阿片受体（κ-OR）介导的信号通路对缺血再灌注（I/R）产生心脏保护作用。将大鼠随机分为四组：对照组、中等强度运动（ME）组、高强度运动（HE）组和急性运动（AE）组。对于运动训练方案，大鼠先进行一周的适应性跑步机训练，从第二周开始，ME组和HE组进行八周的运动训练，AE组进行三天的适应性跑步机训练和一天的剧烈运动。在这些方案之后，将三个运动训练组再分为不同的治疗组，对大鼠进行30分钟的缺血和120分钟的再灌注。运动训练可减少I/R引起的梗死面积和血清心肌肌钙蛋白T（cTnT）的变化。此外，运动训练还可减轻I/R引起的心脏功能障碍。运动训练的这些作用可被nor-BNI（一种选择性κ-OR拮抗剂）、化合物C（一种选择性AMPK抑制剂）、Akt抑制剂和L-NAME（一种非选择性eNOS抑制剂）逆转。ME组、HE组和AE组中κ-OR的表达以及AMPK、Akt和eNOS的磷酸化显著增加。这些发现表明，运动训练的心脏保护作用可能是由κ-OR-AMPK-Akt-eNOS信号通路介导的。
