耐力训练对兔心房颤动的影响及机制探索
Effects of Continuous Training on the Induction of Atrial Fibrillation in a Rabbit Model
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摘要:目的 通过耐力运动训练兔动物模型探索运动相关性心房颤动(AF)的发生机制。方法 36只新西兰大耳兔随机分为对照组、中强度耐力训练组、高强度耐力训练组(每组12只):对照组不做任何耐力训练处理;耐力运动训练组每周训练5 d,每天1 h或一次性力竭(不足1 h),共持续16 周(中强度耐力训练组:坡度0度,速度15 m/min;高强度耐力训练组:坡度0度,速度30 m/min)。训练完成后,各组随机各取6只,共18只兔采用离体心脏Langendorff系统进行灌流,将1 μmol/L乙酰胆碱(Ach)+不同浓度的氯化钡(BaCl2)溶液(0、0.1、0.5、1、3、6 μmol/L)灌入冠脉内,开始持续给药过程中电生理指标的测定及记录。在左心耳置入的电极分别记录相应的心房有效不应期(AERP)及90%动作电位时程(APD90)、并给予心脏期前程序刺激(S1S2)诱发房颤,记录并计算房颤发生率。灌流完后剪取兔左心房,经实时荧光定量(qRT)-PCR 技术检测心房肌组织内向整流钾电流/通道(IK1)kir2.1、kir2.2、胶原蛋白Ⅰ和胶原蛋白Ⅲ的mRNA表达量。取各组剩余6只实验兔,共18只取左心房组织标本, 应用Masson 染色进行组织学检查,测定心肌组织胶原容积分数。结果 长期高强度的运动训练16周后,不同组间,Ach背景相同,BaCl2剂量相同作用下,随着运动强度的增加,APD90、AERP相应缩短, 房颤发生率增加,BaCl2 取0~6 μmol/L时,高强度耐力训练组与其余两组间比较差异均有统计学意义(P<0.001),而其余两组之间差异无统计学意义。同一组内,Ach背景相同,随着BaCl2剂量的增加,APD90、AERP相应延长,房颤发生率降低,3组组内比较,差异均有统计学意义(P<0.05)。随着运动量的增加,兔左心房kir2.1、kir2.2、胶原蛋白Ⅰ和胶原蛋白Ⅲ的 mRNA表达量均增加,胶原容积分数增加,高强度耐力训练组>中强度耐力训练组>对照组,差异有统计学意义(P<0.05)。结论 长期的高强度耐力运动训练可通过增加实验兔心房组织纤维化程度、心肌细胞IK1数量和(或)功能,改变心电传导,促使实验兔房颤发生和维持。Abstract:Objective This study was aimed to assess mechanisms underlying continuous training induced atrial fibrillation (AF) in an animal model.Methods Healthy New Zealand rabbits were divided into three groups (n=12 each): control group (C), moderate intensity group (M), and high intensity group (H). The intensity of continuous training was adjusted according to the treadmill speed. After 12 weeks of training, with a Langendorff perfusion system, AF was induced by S1S2 stimulation and the incidence was recorded. Changes in atrial kir2.1, kir2.2, type Ⅰ and Ⅲ collagen protein mRNA expressions were assessed by quantitative real-time PCR. Masson staining was used to assess the extracellular collagen volume fraction (CVF) .Results After 12 weeks, comparing with group C, groups M and H had greater (P<0.05): CVF, incidence of AF (P<0.05, also between Groups H and M), and atrial inward rectifier potassium current/channel (IK1) . In Group H, kir2.1, kir2.2, type Ⅰ and Ⅲ collagen protein mRNA expressions in the left atrium were increased (P<0.05, compared with Groups C and M).Conclusion Long-term and high-intensity treadmill running could increase AF incidence in rabbits.
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