【作者】 陈峰；

【导师】 王爱玲；

【作者基本信息】 安徽医科大学 ， 内科学， 2011， 硕士

【摘要】 目的:尼可地尔是临床上唯一具有抗心绞痛作用的钾通道开放剂,有较理想的临床疗效和良好的耐受性,可通过开放心肌线粒体KATP通道起到保护心肌的作用,但其作用机制尚未明确。本实验通过完整大鼠模型探讨线粒体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影响极其对线粒体的保护作用。方法:建立大鼠缺血再灌注损伤模型,50只大鼠分为正常对照组(A组),缺血再灌注组(B组):冠脉左前降支闭塞60min,再灌注120min。缺血前给予尼可地尔组(C组):冠脉左前降支闭塞前15min静脉给予尼可地尔5mg/kg,再灌注开始时给予尼可地尔组(D组):冠脉左前降支闭塞60min,再灌注开始时静脉给予尼可地尔5mg/kg。再灌注开始后给予尼可地尔组(E组):再灌注开始后15min静脉给予尼可地尔5mg/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MDA,SOD的含量,测定线粒体膜电位,免疫组化法检测心肌Bcl-2,Bax蛋白表达,并进行电镜检查。抽取大鼠股静脉血,测定静脉血中LDH含量。结果:尼可地尔组(C组、D组、E组)与缺血再灌注组(B组)比较,LDH含量、SOD活性、MDA水平差异均有统计学意义(P<0.01, P<0.05);尼可地尔组(C组、D组、E组)心肌超微结构损伤程度轻;与缺血再灌注组(B组)比较,尼可地尔组(C组、D组、E组)Bcl-2表达上调,Bax表达减弱;与缺血再灌注组(B组)比较,尼可地尔组(C组、D组、E组)线粒体膜电位升高(P<0.05)。结论:尼可地尔在心肌缺血再灌注中能对心肌起到一定的保护作用,其机制可能与激活线粒体ATP敏感性钾通道有关。更多还原

【Abstract】 Aim: Nicorandil has been reported to induce the cardioprotection by opening the mitochondrial KATP channels of the myocardiocytes. Up to now the mechanism of cardioprotection is not fully understood. The purpose of present study was to investigate the cardioprotective effect of nicorandil on the heart ischemia-reperfusion the rats.Methods: 50 rats were randomly divided into 5 groups as follows: Group A: control group Group. B: ischemia-reperfusion group. Group C: nicorandil (5mg/kg) was administrated by intravenous injection at 15 minutes before the artery occlusion. Group D: nicorandil (5mg/kg) was administrated at the onset of the reperfusion. Group E: nicorandil (5mg/kg) was administrated intravenous injection at 15 minutes after the artery occlusion. After the reperfusion, the serum lactate dehydrogenase (LDH) activity, the total superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content of myocardial tissue were measured. The myocardial ultrastructure was observed with electron microscope. 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.Results: The results of the nicorandil groups (group C, D, E) were compared with that of group B, the activity of LDH and the level of MDA decreased and the activity of SOD increased in nicorandil group (P<0.01, P<0.05). The positive staining level of the expressed Bcl-2 was increased, the positive staining level of the expressed Bax was decreased (P<0.01). The mitochondrial membrane potential was increased in the nicorandil groups compared with that of group B (P<0.05). Conclusion: Nicorandil can have a cardioprotective function on the heart with the ischemia-reperfusion in the rats. The cadioprotective effect of nicorandil may be based on the opening of the mitochondrial KATP channel.更多还原