摘要
目的探讨缝隙连接是否参与缺血后处理和庚醇的抗心肌缺血/复灌(I/R)损伤作用。方法采用离体大鼠心脏Langendorff灌流方法,冠脉结扎30min,复灌120min复制局部I/R模型,测定心室力学指标和复灌各时间点冠脉流出液中乳酸脱氢酶(LDH)含量。实验结束测定心肌梗死面积。全心停灌30min,复灌120min复制全心I/R模型,测定心律失常和心肌传导速度。分别在复灌初期给予缝隙连接脱耦联剂庚醇和缝隙连接开放剂AAP10各15min。结果在局部缺血/复灌模型上,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,复灌期间冠脉流出液中LDH含量降低。同时缺血后处理组明显改善心室力学指标,缓解冠脉流量的减少;在全心缺血/复灌模型上,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在局部和全心缺血/复灌模型上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缺血/复灌损伤作用,这种保护作用可能与缝隙连接细胞间通讯的减弱有关。
OBJECTIVE To determine whether the cardioprotection of ischemic postconditioning and heptanol against ischemia/ reperfusion （I/R） is mediated by gap junction. METHODS The isolated perfused hearts of male rats were subjected to 30 min of regional ischemia followed by 120 rain of reperfusion. The infarct size and the level of lactate dehydrogenase （LDH） in the coronary effluent were measured. The arrhythtnia scores and conduction velocity of ventricular myocardium were measured in global ischemia model of rat heart subjected to 30 min of ischemia followed by 120 min of reperfusion. Gap junction uncoupler heptanol and opener antiarrhythmic peptide 10 （AAP10） were administrated at the beginning of reperfusion for 15 min, respectively. RESULTS In the Langendorff perfused rat heart model, ischemic postconditioning （3 cycles of 10 s reperfusion/10 s regional ischemia starting at the beginning of the reperfusion） and heptanol reduced infarct size and LDH release, ischemic postconditioning also improved the recovery of the left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure and rate-pressure product （ left ventficular developed pressure multiplied by heart rate）. Ischemic postconditioning （6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of the reperfusion ） and heptanol reduced arrhythmia scores and conduction velocity of ventricular myocardium. Administration of AAP10 attenuated the cardioprotection of ischemic postconditioning and heptanol. CONCLUSION The cardioprotection of ischemic postconditioning and heptanol may be related to the attenuation of gap junction communication on myocardial ischemia/reperfusion injury.
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2009年第3期187-193,共7页
Chinese Journal of Modern Applied Pharmacy
基金
浙江省自然科学基金资助项目(Y205278)
浙江省绍兴市科技计划项目(2005143)
浙江省绍兴文理学院科研项目(07LG1028)
关键词
缺血后处理
缝隙连接
庚醇
缺血/复灌损伤
心脏
ischemic postconditioning
gap junction
heptanol
ischemia/reperfusion injury
heart
