比较依达拉奉和DIDS在大鼠急性缺血再灌注损伤心肌中的作用  

Effects of edaravone and DIDS on acute myocardial ischemia/reperfusion injury

作　　者：刘艳霞[1] 刘佳妮[1] 沈明志[1] 赵萌[1] 翟雅莉[1] 周洁晶[2] 王晓明[1] 

机构地区：[1]第四军医大学西京医院老年病科,陕西西安710032 [2]第四军医大学西京医院妇产科,陕西西安710032

出　　处：《心脏杂志》2010年第6期811-813,827,共4页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(30770847)

摘　　要：目的:探讨氯离子通道阻断剂4,4′-二异硫氰基芪-2,2′-二磺酸(4,4′-diisothiocyanostilbene-2,2′-disulfonicacid,DIDS)与自由基清除剂依达拉奉(Edaravone,EDRV))在大鼠缺血/再灌注损伤(I/RI)心肌中的作用。方法:建立常规大鼠I/RI(30 min/4 h)模型,实验分为5组:假手术组、I/RI对照组、EDRV组、DIDS组和DIDS+EDRV组,每组8只大鼠(n=8)。再灌注前,给予EDRV(10 mg/kg),给药5 min;再灌注即刻,给予DIDS 4 ml[14 mg/(kg.h)]2 h。于缺血前、后和再灌注后,记录心脏的血流动力学指标:左室收缩压(LVSP)及左室等容收缩/舒张期压力上升或下降最大速率(±dp/dtmax)。再灌注结束时,检测大鼠心肌梗死(MI)面积、血清肌酸激酶(CK)和乳酸脱氢酶(LDH)的活性。结果:与I/RI组相比,DIDS组、EDRV组和DIDS+EDRV组MI面积显著减小(P<0.05);LVSP和±dp/dtmax显著提高(P<0.05),血清CK和LDH的活性显著降低(P<0.05);DIDS组和EDRV组的上述指标无统计学差异;DIDS+EDRV组对心肌的保护作用强于DIDS或EDRV组(P<0.05)。结论:DIDS与EDRV都具有对抗或减轻I/RI心肌的作用,但二者的差异不明显,联合使用具有相加作用。AIM： To investigate the effect of chloride channel inhibitor, 4,4＇-diisothiocyanostilbene-2,2＇- disulfonic acid （DIDS） and free radical scavenger, edaravone （EDRV） , on myocardial ischemia/reperfusion injury （I/RI） in vivo. METHODS： Male Sprague Dawley rats subjected to 30 min of myocardial ischemia and 4 h of repeffusion were divided into five groups： sham group, I/RI group, DIDS group, EDRV group and DIDS ＋ EDRV group （eight rats/group ）. Rats were treated by program-controlled micropump injection of DIDS [ 14 mg/kg, 4 ml/（kg · h）, 2 hi at the beginning of reperfusion, and EDRV （ 10 mg/kg） was injected into intraaortic sinus 5 rain before reperfusion. Changes of left ventricle systolic pressures （LVSP） and the maximal first derivative of developed pressure （ ± dP/dt ） were monitored from the time of myocardial ischemia to the end of reperfusion. Myocardial infarction size, serum creatine kinase （CK） activity, and lactate dehydrogenase （LDH） activity were determined at the end of reperfusion. RESULTS： Compared with those in I/RI groups, DIDS, EDRV or DIDS ＋ EDRV treatment significantly reduced the size of myocardial infarction （ n = 8, P 〈 0. 05 ）. LVSP and ＋ dP/ dtmax were significantly improved in DIDS, EDRV or DIDS ＋ EDRV treatment groups （n = 8, P 〈 0. 05）.Serum CK activity and LDH significantly decreased （ n = 8, P 〈 0. 05 ）. No statistical difference was observed between DIDS and EDRV groups for the above-mentioned results. Compared with DIDS group alone or EDRV group alone, the combined administration of DIDS ＋ EDRV had a stronger cardioprotective effect than DIDS or EDRV alone （ n =8, P 〈 0. 05）. CONCLUSION ： No significant difference has been found in the protective effect of DIDS alone or EDRV alone on myocardial ischemia/reperfusion injury, but combined administration of DIDS and EDRV has a cumulative effect.

关 键 词：4 4'-二异硫氰基芪-2 2’-二磺酸 缺血/再灌注损伤 活性氧簇 依达拉奉 大鼠 

分 类 号：R542.2[医药卫生—心血管疾病]