尼可地尔对大鼠心肌缺血再灌注损伤的保护作用研究  

The protective effect of nicorandil on rat heart ischemia-reperfusion

作　　者：陈峰[1] 王爱玲[1] 徐凤[1] 周美玲[1] 

机构地区：[1]安徽医科大学第一附属医院心血管内科,合肥230022

出　　处：《安徽医科大学学报》2011年第9期923-925,956,共4页Acta Universitatis Medicinalis Anhui

摘　　要：目的探讨线粒体ATP敏感性钾通道开放剂尼可地尔对大鼠心肌缺血再灌注损伤的保护作用。方法建立大鼠缺血再灌注损伤模型,50只SD大鼠随机分为5组:①正常对照组(A组);②缺血再灌注组(B组):冠脉左前降支闭塞60 min,再灌注120 min;③缺血前给予尼可地尔组(C组):冠脉左前降支闭塞前15 min静脉给予尼可地尔5 mg/kg;④再灌注开始时给予尼可地尔组(D组):冠脉左前降支闭塞60 min,再灌注开始时静脉给予尼可地尔5 mg/kg;⑤再灌注开始后给予尼可地尔组(E组):再灌注开始后15 min静脉给予尼可地尔5 mg/kg。再灌注结束后留取各组大鼠缺血再灌注区心肌组织,测定丙二醛(MDA)、超氧化物歧化酶(SOD)的含量,测定线粒体膜电位,抽取大鼠股静脉血、测定乳酸脱氢酶(LDH)含量。免疫组化法检测心肌Bcl-2、Bax蛋白表达,并进行电镜检查。结果与B组比较,C、D、E组LDH含量降低、SOD活性升高、MDA水平降低,差异均有统计学意义(P<0.01,P<0.05)。与B组比较,C、D、E组Bcl-2表达升高,Bax表达下降(P<0.01,P<0.05),线粒体膜电位升高(P<0.05)。C、D、E组心肌超微结构损伤程度轻。结论尼可地尔在心肌缺血再灌注损伤中对心肌起到一定程度的保护作用,其机制可能与激活线粒体ATP敏感性钾通道有关。Objective To investigate the cardioprotective effect of nicorandil on the heart ischemia-reperfusion in rats.Methods 50 rats were randomly divided into 5 groups as follows： group A： control group,group B： ischemia-reperfusion group,group C： nicorandil（5 mg/kg） was administrated by intravenous injection at 15 min before the artery occlusion,group D： nicorandil（5 mg/kg） was administrated at the onset of the reperfusion,group E： nicorandil（5 mg/kg） was administrated intravenous injection at 15 min after the artery occlusion.After the reperfusion,the serum lactate dehydrogenase（LDH） and total superoxide dismutase（SOD） activity and the malondialdehyde（MDA） content of myocardial tissue were measured.The expression of the anti-apoptotic protein Bcl-2 and the apoptotic protein Bax were detected by immunohistochemical staining.The mitochondrial membrane potential was detected by spectrophotometer.The myocardial ultrastructure was observed with electron microscope.Results Compared with that of group B,the activity of LDH and the level of MDA decreased and the activity of SOD increased in group C,D and E,which were treated with nicorandil（P0.01,P0.05）.The positive staining level of Bcl-2 was increased,Bax was decreased（P0.01,P0.05）.Compared with group B,the mitochondrial membrane potential was increased in group C,D and E（P0.05）.Myocardial ultrastructure injury was decreased in group C,D and E.Conclusion Nicorandil has a cardioprotective function on the heart with the ischemia-reperfusion in the rats which may be related to the opening of the mitochondrial KATP channel.

关 键 词：尼可地尔 心肌再灌注损伤 细胞凋亡 膜电位 线粒体 

分 类 号：R972.3[医药卫生—药品] R329.25[医药卫生—药学]