瑞芬太尼预处理对心力衰竭大鼠心肌的保护作用

Cardioprotective effect of remifentanil preconditioning on hearts in heart failure rat

目的探讨瑞芬太尼预处理对阿霉素心衰大鼠离体心肌缺血/再灌注损伤的作用。方法 60只成年♂SD大鼠(250±20)g,尾静脉注射阿霉素2μg·g-1,每周1次,共6周,制成阿霉素心衰大鼠模型。随机将阿霉素心衰大鼠分为6组:对照组(Sham组)、缺血/再灌注组(I/R组)、缺血预处理组(IPC组)、10μg·L-1瑞芬太尼预处理组(RPC 1组)、30μg·L-1瑞芬太尼预处理组(RPC 2组)、60μg·L-1瑞芬太尼预处理组(RPC 3组)。采用Langendorff离体大鼠心肌灌注模型。除Sham组为持续灌注165 min外,所有心脏予以30 min缺血,90 min再灌注。IPC组在缺血前结扎左冠状动脉5 min,松开5 min,共3个循环。RPC组在缺血前给予含浓度分别为10、30、60μg·L-1的瑞芬太尼的K-H液灌注5 min后改用不含瑞芬太尼的K-H液灌注5 min,共3个循环。记录各组心脏在平衡末、再灌5 min、再灌30 min、再灌90 min时的心率(HR)、左室发展压(LVDP)和左室压力升高或降低最大速率(±dp/dtmax)、冠脉流量(CF)并测定冠脉流出液中乳酸脱氢酶(LDH)的活性。再灌末TTC法计算心肌缺血梗死区(IS/AAR)。Western blot半定量检测p-Akt和总Akt的含量。结果平衡灌注末各组间心功能指标(基础值)差异未见统计学意义(P>0.05)。再灌5、30、90 min时,RPC 2组和RPC 3组的LVDP、±dp/dtmax、CF较I/R组高,LDH值较I/R组低(P<0.05)。灌注结束后,见RPC 2组、RPC 3组的IS/AAR较I/R小,p-Akt表达水平升高(P<0.05),而IPC组和RPC 1组的各项指标较I/R组无差异。结论 RPC在一定程度上减轻阿霉素心衰大鼠心肌缺血/再灌注损伤,而缺血预处理对阿霉素心衰大鼠心肌缺血/再灌注损伤无明显保护作用。

Aim To investigate the effects of remifentanil precondioning on adriamycin heart failure following ischemia-reperfusion in isolated rat hearts.Methods All 60 adult male SD rats received 2 μg·g-1 adriamycin as an intravenous tail vein infusion once a week for 6 weeks at a total dose of 12 μg·g-1 to establish an adriamycin-induced chronic heart failure model.60 heart failure rats were randomly divided into 6 groups（10 each）： control group（Sham）,ischemia-reperfusion group（I/R）,ischemic preconditioning group（IPC）,10 μg·L-1 remifentanil precondioning group（RPC 1）,30 μg·L-1 remifentanil precondioning group（RPC 2）,60 μg·L-1 remifentanil precondioning group（RPC 3）.All hearts were linked to the Langendorff apparatus.Left ventricular developed pressure（LVDP）,±dp/dtmax,heart rate（HR）,coronary effluent（CF） were recorded and LDH were measured at the end of equilibration and 5 min,30 min,90 min of reperfusion.Myocardial infarct size were measured with TTC staining at the end of reperfusion.After reperfusion,phosphor-Akt and total Akt were determined by Western blot analysis.Results No differences in baseline hemodynamics and LDH were observed among the groups（P〉0.05）.Compared with group I/R,group RPC 2 and group RPC 3 resulted in a significantly improved functional recovery and had a significant increase in LVDP,±dp/dtmax,CF and a significant decrease in IS（P〈0.05）.Meanwhile,group RPC 2 and group RPC 3 also markedly increased the expression of p-Akt compared with group I/R.Conclusions 30 and 60 μg·L-1 remifentanil preconditioning may effectively protect the hearts against ischemia-reperfusion injury in adriamycin-induced chronic failure isolated rat hearts by activating PI3K/Akt signal pathway.