水通道蛋白4在瑞芬太尼后处理对成人心肌低氧复氧损伤保护中的作用

Role of aquaporin-4 in mediating protective effect of remifentanil postconditioning against adult myocardial hypoxia/reoxygenation injury

目的通过构建成人心肌低氧复氧(H/R)损伤模型,观测瑞芬太尼后处理对成人心肌H/R损伤的保护效应,并探讨水通道蛋白4(AQP-4)在此效应中的作用。方法成人右心耳肌小梁低氧90 min/复氧120 min,低氧结束前10 min开始分别灌注瑞芬太尼0.01,0.1或1.0 nmol·L-1至复氧开始后10 min停止。实验期间,连续监测肌小梁的收缩张力。实验结束后,Western印迹法检测AQP-4蛋白表达。结果与正常对照组相比,H/R组低氧处理30 min后,肌小梁的收缩张力值明显降低(P<0.05),90 min时降至最低;瑞芬太尼0.1 nmol·L-1组150和180 min时张力值均高于H/R组(P<0.05);瑞芬太尼1.0 nmol·L-1组120,150,180和210 min时,张力值均高于H/R组(P<0.05)。与正常对照组相比,H/R组心肌AQP-4表达水平明显增高(P<0.05);与H/R组比较,瑞芬太尼0.1和1.0 nmol·L-1组心肌AQP-4的表达水平下调(P<0.05)。结论瑞芬太尼可减轻成人心肌H/R损伤,其作用机制可能与AQP-4表达降低有关。

OBJECTIVE To investigate the effect of remifentanil postconditioning on myocardial hypoxia/reoxygenation(H/R)injury in adults,and to further explore the role of aquaporin-4(AQP-4)in mediating this effect.METHODS Trabecular muscles from the right atrial appendage of adults were treated with hypoxia for 90 min,followed by reoxygenation for 120 min.Then,remifentanil 0.01,0.1 and 1.0 nmol·L-1 was infused 10 min before the end of hypoxia until 10 min after the start of reoxygenation.The contractile tension of the trabecular muscles was monitored during the experiment.Western blotting was performed to evaluate AQP-4 expression at the end of the experiment.RESULTS Compared with normal control group,muscle tension decreased significantly after 30 min of induction in H/R group(P<0.05),and it was reduced to the minimum at 90 min.The muscle tension at 150 min and 180 min in remifentanil 0.1 nmol·L-1 group was higher than that in H/R group(P<0.05).The muscle tension in remifentanil 1.0 nmol·L-1 group was higher than that in H/R group during reoxygenation(P<0.05).Compared with normal control group,the expression of AQP-4 protein in H/R group was significantly higher(P<0.05),whereas the expression of AQP-4 in remifentanil 0.1 and 1.0 nmol·L-1 groups was down-regulated compared with H/R group(P<0.05).CONCLUSION Remifentanil can alleviate myocardial H/R injury in adults,and its effect may be related to the decreased expression of AQP-4.