缝隙连接通讯对大鼠心脏缺血后处理的心肌保护作用的影响

EFFECT OF GAP JUNCTION ON THE CARDIOPROTECTION OF ISCHEMIC POSTCONDITIONING IN RAT HEART

目的:探讨缝隙连接是否参与心脏缺血后处理和庚醇的抗心肌缺血/复灌损伤作用。方法:在体大鼠实验模型,结扎冠脉30 min,复灌120 min,在停灌后复灌即刻立即给予3次复灌/缺血循环,每次各10 s,共计1 min实现缺血后处理,测定心肌梗死面积和心律失常,观察缺血后处理和缝隙连接脱耦联剂庚醇(0.03、0.06、0.30、0.60 mg/ kg)及其开放剂AAP10(10 mg/kg)对缺血/复灌心肌的作用。离体大鼠心脏实验采用Langendorff灌流方法,全心停灌30 min,复灌120 min,在停灌后复灌即刻立即给予6次全心复灌/停灌循环,每次10 s共计2 min实现缺血后处理,测定心律失常和心肌传导速度,观察缺血后处理和庚醇(0.05、0.10、0.50、1.00 mmol/L)及AAP10(1×10^(-7)mol/L)对缺血/复灌心肌的作用。结果:在在体大鼠缺血/复灌(I/R)模型上,与I/R组相比,缺血后处理组和庚醇组心肌梗死面积明显减少,复灌期间的心律失常评分明显下降;在离体心脏I/R模型上,缺血后处理组和庚醇组在复灌期间的心律失常评分明显下降,心肌传导速度降低。AAP10在在体和离体大鼠心脏模型上均明显减弱缺血后处理和庚醇的心肌保护作用。结论:缺血后处理和庚醇具有抗心肌I/R损伤作用,这种保护作用可能与缝隙连接细胞间通讯的减弱有关。

Aim： To determine whether the cardioprotection of ischemie postconditioning and heptanol in ischemic heart against ischemia/reperfnsion （I/R） is mediated by gap junction. Methods： The effect of ischemic postconditioning, heptanol at different doses（0.03, 0.06, 0.30, and 0.60 mg/kg） and AAP10（ 10 mg/kg） on the intact rat heart during 30 min ischemia and 2 h of reperfusion was observed. Ischemic postcondi- tioning was achieved by 3 cycles of 10 s repeffusion/10 s regional ischemia starting at the beginning of the reperfusion. The infarct size and the arrhythmia scores were measured. The effect of ischemic postconditioning, heptanol at different doses（0.05, 0.10, 0.50 and 1.00 mmol/L） and AAP10（ 1 ×10^-7mol/L） on the isolated heart during 30 min ischemia and 2 h of reperfusion was observed. Ischemic postconditioning was achieved by 6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of the reperfusion. The arrhythmia scores and conduction velocity of ventricle muscle were measured. Results： In the intact rat heart model, ischemic postconditioning and heptanol reduced infarct size and arrhythmia scores. In the Langendorff perfused rat heart model, ischemic postconditioning and heptanol reduced arrhythmia scores and conduction velocity of ventricle muscle. Administration of AAP10, an opener of gap junction attenuated the cardioprotection of ischemic posconditioning and heptanol. Conclution： The cardioprotection of ischemic postconditioning and heptanol may be related to the attenuation of gap junction communication on myocardiac ischemia/reperfusion injury.