摘要
目的:观察氯离子通道阻断剂4,4′-二异硫氰基芪-2,2′-二磺酸(DIDS)与自由基清除剂依达拉奉(EDRV)对急性缺血再灌注损伤(I/RI)心肌组织活性氧水平的影响。方法:心脏常规I/RI(30min/4h)模型分为5组:假手术组、I/RI组、EDRV组、DIDS组和DIDS+EDRV组。再灌注前给予EDRV(10mg/kg)5min;再灌注即刻给予DIDS(14mg/kg,4mL·kg^(-1)·h^(-1))2h。再灌注结束时取心肌组织,检测组织中活性氧(ROS)、羟自由基(OH·)和超氧自由基阴离子(O_2^-),TUNEL法检测心肌细胞凋亡,比色法检测血清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:(1)与I/RI组比较,DIDS组、EDRV组及DIDS+EDRV组中心肌细胞凋亡指数明显降低(P<0.05),ROS、O_2^-、OH·和MDA含量均明显降低(P<0.05),SOD活性均明显增加(P<0.05)。(2)DIDS组与EDRV组相比,EDRV组的ROS、O_2^-、OH·含量和MDA含量降低更显著(P<0.05),但SOD活性增高更显著(P<0.05),心肌细胞凋亡指数无显著差异(P>0.05)。(3)DIDS+EDRV组比DIDS组和EDRV组心肌细胞凋亡指数明显降低(P<0.05);O_2^-、OH·和MDA含量均降低,SOD活性均增加,但无显著差异(P>0.05)。结论:氯离子通道阻断剂DIDS与自由基清除剂EDRV保护心脏作用通过抑制ROS活性水平,减少心肌细胞凋亡,二者联合使用保护心脏作用更强。
AIM：To investigate the effects of chloride channel inhibitor 4,4＇-diisothiocyanostilbene-2,2＇- disulfonic acid（DIDS）and free radical scavenger edaravone（EDRV）on the production of reactive oxygen species in acute ischemia-reperfusion injured（I/RI）myocardium.METHODS：Male Sprague-Dawley rats,subjected to myocardial ischemia for 30 min and reperfusifor for 4 h,were divided into 5 groups：sham group,I/RI group,DIDS group,EDRV group and DIDS ＋ EDRV group.The rats were treated with EDRV（10 mg/kg for 5 min）before reperfusion or/and DIDS （14 mg/kg,4 mL·kg^（-1）·h^（-1）for 2 h）at the beginning of reperfusion by a program-controlled injection micropump. The myocardiac tissues were collected immediately at the end of reperfusion.The levels of ROS,OH· and O_2^- were determined by the methods of spectrofluorophotometry and colorimetry.Myocardial apoptosis was detected by TUNEL method. Serum superoxide dismutase（SOD）activity and malondialdehyde（MDA）concentration were measured by colorimetry. RESULTS：Compared with I/RI group,myocardial apoptotic index,the levels of ROS,O2- OH· and MDA were significantly reduced,and SOD activity was significantly increased in DIDS group,EDRV group and DIDS ＋ EDRV group（P0.05）.Compared with DIDS group,the levels of ROS,O2-,OH· and MDA were significantly decreased,and SOD activity was significantly increased in EDRV group（P〈0.05）.No statistical difference of myocardial apoptotic index between these two groups was observed（P〉0.05）.Compared with DIDS ＋ EDRV group,myocardial apoptotic index in DIDS group and EDRV group was significantly increased（P〈0.05）,and no significant difference of ROS,O2-,OH ·,MDA and SOD between the two groups was found（P〉0.05）.CONCLUSION：DIDS and EDRV protect myocardial cells from apoptosis by inhibition of ROS activity.Combinative use of the two reagents has stronger cardioprotectiue effect,suggesting that they have different regulatory pathways.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2011年第4期648-652,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.30770847
No.81070127)
