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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

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第6期
页码:
811-813,827
栏目:
基础研究
出版日期:
2010-08-23

文章信息/Info

Title:
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
第四军医大学:1.西京医院老年病科，2.西京医院妇产科,陕西 西安 710032
Author(s):
LIU Yan-xia1;  LIU Jia-ni1;  SHEN Ming-zhi1;  ZHAO Ming1;  ZHAI Ya-li1;  ZHOU Jie-jing2;  WANG Xiao-ming1
1.Department of Geriatrics, Xijing Hospital, 2.Department of Obstetrics and Gynecology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
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
Keywords:
4; 4′-diisothiocyanostilbene-2; 2′-disulfonic acid;  ischemia/reperfusion injury;  reactive oxygen species;  edaravone
分类号:
R542.2
DOI:
-
文献标识码:
A
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′-disulfonic acid，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(10mg/kg)，给药5min；再灌注即刻，给予DIDS 4ml［14mg/(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。
Abstract:
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 reperfusion 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 h］ at the beginning of reperfusion, and EDRV (10 mg/kg) was injected into intraaortic sinus 5 min before reperfusion. Changes of left ventricle systolic pressures (LVSP) and the maximal first derivative of developed pressure (±dP/dtmax) 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.

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备注/Memo

备注/Memo:
收稿日期：2009-12-29.基金项目：国家自然科学基金项目资助 (30770847) 通讯作者：王晓明，主任医师，主要从事心血管病的研究Email：xmwang@fmmu.edu.cn 作者简介：刘艳霞，硕士生Email：yanxia306 @126.com
更新日期/Last Update: 2010-08-22